Diagnostic Tools for Dry Eye Disease

European Ophthalmic Review, 2016;10(2):101–7 DOI: https://doi.org/10.17925/EOR.2016.10.02.101

Abstract:

Dry eye disease is multifactorial in aetiology and complex in pathophysiology that makes its diagnosis clinically challenging. Although there are numerous tools for assessment of dry eye disease, no single test is sufficient for the diagnosis. Typically a combination of subjective symptoms and objective tests are used. The aim of this article is to review the available tests, including traditional tools and emerging technologies. This review will include a description of the test methodology, type of data collected, diagnostic reliability of data, benefits and limitations of each test, expected outcomes and tips for practical application.
Keywords: Dry eye disease, dry eye diagnosis, tear film
Disclosure: Sarah Dougherty Wood and Shahzad I Mian do not have financial or proprietary interest in any materials or methods mentioned. No funding was received in the publication of this article.
Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.
Acknowledgments: To be confirmed by Shahzad I Mian and Sarah Dougherty Wood.
Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.
Received: November 02, 2016 Accepted December 07, 2016
Correspondence: Shahzad I Mian, WK Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI, 48105, US. E: smian@umich.edu
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

The International Dry Eye Workshop Dry Eye Workshop (DEWS) defined dry eye as “a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage of the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface”.1 This condition is divided into two general types: deficient aqueous production by the lacrimal gland and increased evaporation of the tear film, with the latter being more prevalent. It is also common for patients to exhibit a combination of both types of dry eye disease. Despite the seemingly clear definition of the disease, the diagnosis presents many challenges to the practitioner. First, no gold standard protocol for diagnosis exists2 and no one test is sufficient for diagnosis due to poor reliability for many common tests, multiple causative components of the disease and lack of well-defined cut-off values to distinguish disease from normal.2 To further complicate the diagnosis, the signs and symptoms do not always correlate and both can vary based on influences, such as diurnal or seasonal fluctuations.3 In addition, many of the tests are invasive in nature and this may influence the outcome. Lastly, other conditions can mimic dry eye such as ocular allergy. Due to these challenges, alternatives to traditional dry eye testing have emerged. The purpose of this article is to describe the traditional and emerging tests for diagnosis that are clinically useful, including the benefits and limitations and practical pearls. Table 1 lists both the traditional and emerging tests categorised by test objective.

Traditional tests
Symptom questionnaires

Subjective symptoms and their quality of life impact are a critical component of dry eye evaluation. The clinical signs and symptoms do not always correlate and the patients’ experience of their condition is ultimately the most important measure and will cause them to seek treatment. Symptom questionnaires are one of the most repeatable of the dry eye diagnostic tests4 and allow for diagnosis screening, assessment of treatment efficacy and grading of disease severity. Symptom questionnaires are also a critical part of dry eye clinical research trials. The Ocular Surface Disease Index (OSDI) is commonly used, validated and includes 12 questions related to experience during the previous week regarding ocular symptoms, the severity, how these affect visual function and the ocular response to environmental triggers. The score can range from 0–100 with a higher score being worse. A score of 15 has moderate sensitivity and specificity, 60% and 83%, respectively, for the diagnosis of dry eye disease.5 The Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire helps identify symptoms and focuses on their severity and frequency.6 Table 2 provides a summary of popular questionnaires including links to obtain the questionnaires for use.

Practical pearls
• Symptom questionnaires should be used in combination with objective findings to aid in diagnosis.
• These questionnaires can easily be given by a trained technician.
• The The International Dry Eye Workshop Dry Eye Workshop (DEWS) report recommends adopting one of the questionnaires to be used routinely in the clinic setting for screening purposes.4

Schirmer test
The Schirmer test is a common, cheap and easy clinical test to perform to indirectly measure tear production. There are several versions of this test but the most common are the Schirmer 1 without topical anaesthetic and a variation with anaesthetic. Schirmer with anaesthetic measures the basal aqueous tear production and without anaesthetic additionally measures reflex tearing. The test begins with the application of a filter paper test strip in the inferior temporal conjunctival sac of both eyes. If anaesthetic is applied, the inferior fornix should be blotted to remove residual fluid. The strip is removed after 5 minutes and the length of the tear wetting is measured in millimeters. A reading of 10 mm or greater is generally considered the cut-off for a normal value for both tests. An abnormal finding is highly suggestive of aqueous deficient dry eye. This test suffers from variable repeatability and a wide range of sensitivity and specificity values but the accuracy seems to increase as the severity of the disease increases.2

Practical pearls
• No consensus has been established as to whether the eyes should be open or closed during testing.2
• This test should be performed after conjunctival and corneal stain tests because the testing strip may disrupt these surfaces and alter their accuracy.
• A 1-minute Schirmer test has been proposed to reduce patient discomfort and speed up the test. In this variant, severe dry eye is considered 2 mm and mild to moderate is 3–6 mm.2
• Avoid punctal plugs as a treatment for dry eye in patients with test results above 10. They have a higher risk of excessive tearing as a result.

Phenol red thread test
The phenol red thread test is another, less-common, measure of tear production. This variation is more appealing compared with the Schirmer test because it is less irritating and has only a 15-second test duration, but the downside is that it is technically harder to perform. A cotton thread that contains phenol red dye is placed in the same location as the Schirmer test and no anaesthetic is used (see Figure 1). The alkaline pH of the tears causes the dye to turn from yellow to red and then the length of the tear wetting is measured in millimeters. The cut-off value for normal is 10 mm or greater. There is controversy about the accuracy of this test compared with the Schirmer test.2

The International Workshop on Meibomian Gland Dysfunction notes that "if testing suggests the diagnosis of a generic dry eye and tests of tear flow and volume are normal, then evaporative dry eye is implied, and quantification of MGD will indicate the meibomian gland’s contribution".7

Tear break-up time
Tear break-up time (TBUT) is common, cheap and easy to perform. This test is performed to determine tear film stability, specifically local evaporation from the tear film surface.3 A fluorescein strip is moistened with saline and placed in the inferior cul-de-sac. For best accuracy, this test should occur before any eye drops have been used or the lids manipulated. The patient is observed with a cobalt blue filter and diffuse illumination at the slit lamp. The time (in seconds) between a blink and the appearance of a dark spot in the fluorescein is the TBUT. The patient should be allowed to blink freely prior to the test because forced blinking can cause reflex tearing and affect the accuracy. The test should be repeated three times and the average used to obtain the most reliable result. Ten seconds or greater is considered normal. Abnormal results can occur in evaporative and aqueous deficient forms of dry eye. This test has been criticised because the fluorescein itself can cause tear film instability and give a falsely low result. The non-invasive TBUT (NI-TBUT) test will be discussed later in this article.

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Keywords: Dry eye disease, dry eye diagnosis, tear film