Diagnosis of dry eye disease and emerging technologies

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Abstract

Dry eye is one of the most commonly encountered problems in ophthalmology. Signs can include punctate epithelial erosions, hyperemia, low tear lakes, rapid tear break-up time, and meibomian gland disease. Current methods of diagnosis include a slit-lamp examination with and without different stains, including fluorescein, rose bengal, and lissamine green. Other methods are the Schirmer test, tear function index, tear break-up time, and functional visual acuity. Emerging technologies include meniscometry, optical coherence tomography, tear film stability analysis, interferometry, tear osmolarity, the tear film normalization test, ocular surface thermography, and tear biomarkers. Patient-specific considerations involve relevant history of autoimmune disease, refractive surgery or use of oral medications, and allergies or rosacea. Other patient considerations include clinical examination for lid margin disease and presence of lagophthalmos or blink abnormalities. Given a complex presentation and a variety of signs and symptoms, it would be beneficial if there was an inexpensive, readily available, and reproducible diagnostic test for dry eye.

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Most cited references 95

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The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee.

Alan Tomlinson, Anthony Bron, Donald R Korb … (2011)

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The lack of association between signs and symptoms in patients with dry eye disease.

Kelly Nichols, Jason J. Nichols, G Lynn Mitchell (2004)

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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Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease.

A Solomon, D Dursun, Z Liu … (2001)

To compare the expression of the pro- and anti-inflammatory forms of interleukin (IL)-1 in the tear fluid and conjunctival epithelium of normal eyes and those with dry-eye disease. The concentrations of IL-1 alpha, IL-1 beta (precursor and mature forms), and IL-1 receptor antagonist (IL-1Ra) were measured by ELISA in tear fluid samples obtained from normal individuals and patients with dry eye who had rosacea-associated meibomian gland disease (MGD) or Sjögren's syndrome (SS) aqueous tear deficiency (ATD). These cytokines were also measured in normal tear fluid before and after nasal stimulation to induce reflex tearing. The relative expression of these cytokines was evaluated in conjunctival impression cytology specimens and conjunctival biopsy tissue obtained from normal subjects and SS ATD-affected patients using immunofluorescent staining. Matrix metalloproteinase (MMP)-9 concentration and activity in the tear fluid were evaluated with gelatin zymography and with an MMP-9 activity assay kit, respectively. Compared with normal subjects, the concentration of IL-1 alpha and mature IL-1 beta in the tear fluid was increased, and the concentration of precursor IL-1 beta was decreased in patients with MGD (P < 0.05, P = 0.02, and P < 0.01, respectively) and SS ATD (P < 0.001, P = 0.02, and P < 0.001, respectively). There was no significant change in the concentration of IL-1 alpha, precursor IL-1 beta, and IL-1Ra in reflex tear fluid, indicating that the lacrimal glands may secrete these cytokines. The activity of MMP-9, a physiological activator of IL-1 beta, was significantly elevated in the tear fluid of both dry-eye groups compared with normal subjects. A strong positive correlation was observed between the intensity of corneal fluorescein staining and the tear fluid IL-1 alpha concentration (r(2) = 0.17, P < 0.02) and the mature-to-precursor IL-1 beta ratio (r(2) = 0.46, P < 0.001). Positive immunofluorescent staining for IL-1 alpha, mature IL-1 beta, and IL-1Ra was observed in a significantly greater percentage of conjunctival cytology specimens from eyes with SS ATD than in those from normal eyes (P < 0.01 for IL-1 alpha, P < 0.009 for mature IL-1 beta, and P < 0.05 for IL-1Ra). Dry-eye disease is accompanied by an increase in the proinflammatory forms of IL-1 (IL-1 alpha and mature IL-1 beta) and a decrease in the biologically inactive precursor IL-1 beta in tear fluid. Increased protease activity on the ocular surface may be one mechanism by which precursor IL-1 beta is cleaved to the mature, biologically active form. The conjunctival epithelium appears to be one source of the increased concentration of IL-1 in the tear fluid of patients with dry-eye disease. These results suggest that IL-1 may play a key role in the pathogenesis of keratoconjunctivitis sicca.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Ophthalmol

Journal ID (iso-abbrev): Clin Ophthalmol

Journal ID (publisher-id): Clinical Ophthalmology

Title: Clinical Ophthalmology (Auckland, N.Z.)

Publisher: Dove Medical Press

ISSN (Print): 1177-5467

ISSN (Electronic): 1177-5483

Publication date Collection: 2014

Publication date (Electronic): 20 March 2014

Volume: 8

Pages: 581-590

Affiliations

[1 ]The Dry Eye Center at Physician Eyecare of New York, New York, NY, USA

[2 ]New York Eye and Ear Infirmary, New York, NY, USA

[3 ]Laser and Corneal Surgery Associates, New York, NY, USA

Author notes

Correspondence: Robert Latkany, Dry Eye Clinic, New York Eye and Ear Infirmary, The Dry Eye Center at Physician Eyecare of New York, 150 East 32nd Street 102, New York, NY 10016, USA, Tel +1 212 689 2020, Email relief@ 123456dryeyedoctor.com

Article

Publisher ID: opth-8-581

DOI: 10.2147/OPTH.S45444

PMC ID: 3964175

PubMed ID: 24672224

SO-VID: df240400-7394-4122-bd43-7ea9111288bb

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.

Diagnosis of dry eye disease and emerging technologies

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Most cited references 95

The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee.

The lack of association between signs and symptoms in patients with dry eye disease.

Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease.

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