Article

BE THE DED DETECTIVE

Learn about the diagnostic tests that can aid you in identifying this chronic and bothersome condition

DED is the most prevalent medical condition we will encounter in optometric practice.1 Because of the impact DED has on our patients’ quality of vision (blurriness) and life (its symptoms of foreign body sensation, photophobia, etc. distract from and hinder life’s pleasures), we must be vigilant in identifying it in our patients. Also, as the TFOS DEWS II highlighted, there can be a mismatch between signs and symptoms that may be attributed by the neurosensory component of DED.

Here, we discuss the importance of patient history and the diagnostic tests that can aid us in arriving at the DED diagnosis, organized by the three disease types: (1) both aqueous-deficient and evaporative DED, (2) just aqueous-deficient DED or (3) just evaporative DED.

Corneal staining shows DED.
Photo courtesy of Vin Dang, O.D.

PATIENT HISTORY

An efficient case history is critical, as it leads you to your choices of diagnostic testing.

For example, patients who have autoimmune disease (lupus, rheumatoid arthritis, etc.) are more likely to fall into the aqueous-deficient DED category. Granted, some patients may have autoimmune disease, and the systemic condition may not be diagnosed yet. Thus, asking questions about joint pain and fatigue may be beneficial and elicit a referral to their primary care doctor or rheumatologist for further assessment.

If no clear path is determined based on the patient’s history, you could mix and match the aqueous-deficient DED and evaporative DED diagnostics to cast a slightly wider net.

For example, performing a phenol red thread test and evaluating the glands’ expressibility at the slit lamp can provide efficient insights, and neither require a lot of time or investment.

All this said, simply playing the odds, the patient is more likely to have an evaporative type of DED.2

BOTH

The following five diagnostic tests can be used:

  1. DED patient questionnaire. Organization-validated DED questionnaires (The Dry Eye Questionnaire 5 [DEQ-5], Standardized Patient Evaluation of Eye Dryness and Ocular Surface Disease Index [SPEED]) can elicit symptoms — such as blurred/fluctuating vision, burning, stinging and/or watery eyes — from patients who are at risk for DED, but who may not have been aware of their symptoms.
    For our practices, DED questionnaires are some of the best tools we utilize because they give us measurements of our patients’ subjective symptoms, enabling us to determine whether additional testing is warranted.
  2. Vital dyes. Vital dyes enable us to measure ocular surface health. Sodium fluorescein (NaFl) highlights any break on the corneal epithelium caused by DED-induced micro-abrasion or desiccation. NaFl also can be used to measure TBUT and, thus, tear film stability. Lissamine green is effective to check for devitalized cells on the conjunctiva.3 Patients who present with moderate conjunctival staining or mild corneal staining would be categorized as Level 2 or as having moderate DED, according to the Delphi Panel.4 More recently, the TFOS DEWS II recommended both lissamine green and NaFl in the clinical protocol for the DED test battery.
  3. Metalloproteinase-9 (MMP-9) in-office test. This point-of-care test assesses the tears for elevated levels of MMP-9, a nonspecific inflammatory marker consistently present in patients who have DED.5 MMP-9 levels greater than 40 ng/ml are indicative of a positive test, or DED.6 By collecting a sample of the patient’s tears and placing them in a buffered solution, results are available within 10 minutes.
  4. Tear osmolarity test. This measures the salt amount, or osmolarity, in tears. Osmolarity readings above 308 mOsms/L or an inter-eye difference of >8 mOsm are an indication of mild hyperosmolarity and loss of homeostasis, which is usually indicative of DED and an unstable tear film.7,8 A caveat: If osmolarity testing is considered, TBUT should be evaluated after it in those suspected of having evaporative DED, because the introduction of NaFl dye into the tear composition can alter the osmolarity.
  5. Corneal topography. Patients suspected of having DED on topography can be identified by any abnormal spots (isolated steepening or flattening), asymmetric mean K values and irregular mires on the placido disc. In addition, this device allows for an objective measurement of the tear film, providing abnormal values <10 seconds using various technology. One instrument uses the reflection of the tear film and a computer algorithm to determine the TBUT. Another device measures it by detecting localized breaks in the tear film using infrared waves. A new player offers tear film analysis via assessing the point spread function and the TBUT. Direct fluorescein staining at the outer canthus and measurements taken between one to three seconds after instillation can be used to determined TBUT.

AQUEOUS-DEFICIENT

The following five diagnostic tests can be used:

  1. Schirmer’s Test. This test measures and quantifies tear volume via a thin absorbent strip of paper placed on to the lid margin. Tear secretion is measured on the strip after five minutes, with 15 mm or greater in tear secretion considered normal. A topical anesthetic can be given to patients to prevent reflex tearing.
  2. Phenol red thread test. This is a more comfortable form of Schirmer’s. It is faster and causes less reflex tearing. A simple thread is attached to the patient’s lid, and the results can be obtained after 15 seconds.
  3. Slit lamp biomicroscopy. This enables you to assess the tear meniscus height (TMH). You grade the inferior tear prism height as minimal, normal or excessive. The normal average TMH is 0.20 mm. Any measurement lower indicates a decreased tear volume, or aqueous-deficient DED. Several pieces of diagnostic equipment have algorithms to measure the TMH.
  4. AS-OCT. Anterior segment OCT can be utilized to measure the TMH quantitatively in a non-contact, non-biased, non-invasive method. The sensitivity and specificity of TMH value with AS-OCT for DED diagnosis is 77.8% and 71.7%.9
  5. Sjögren’s syndrome test. This test uses traditional (SS-A [RO], SS-B [La], etc.) and novel proprietary biomarkers (SP-1, IgA, IgC, IgM, etc.) to provide the Sjögren’s syndrome diagnosis via an in-office blood test or through a local lab. With earlier diagnosis, patients can be monitored for organ-specific manifestations, such as interstitial pneumonitis. It is also important to be on the lookout for non-Hodgkin lymphoma.10
    Common symptoms for patients who have Sjögren’s syndrome include dry mouth, hyperhidrosis and dry eyes. We frequently order this test for all our DED patients.

EVAPORATIVE

The following three diagnostic tests can be used:

  1. Meibography. A major component of evaporative DED is meibomian gland dysfunction (MGD). Meibography is an infrared analysis of the meibomian glands. There are two types of meibography: contact and non-contact.
    Contact meibography involves a direct light source to evert the lower lid and a specialized camera to image the meibomian glands.
    Non-contact meibography uses an infrared filter and an infrared charge-coupled device video camera to image a digitally everted eyelid.
    Images taken with meibography help patients to understand how the meibomian glands affect their disease. Grading for MGD structure ranges from 0, no gland loss, to 3, >67% gland loss.11
  2. Meibomian gland expression. After obtaining the anatomical structure of the meibomian glands, it is equally important to address the quality and quantity of meibomian gland secretions as part of the slit lamp evaluation (expression). To do so, you can use your fingers, a cotton swab or a device. The quality of the meibum expression will be graded from 0, or clear, to 3, or inspissated /toothpaste-like, indicating MGD.12 The more advanced the characteristics and expressibility, the more progressive the diagnosis.13 Low lipid layer thickness has been shown to be correlated with expressible meibomian glands that would suggest a higher probability for MGD.14
  3. Blink rate measuring device. Blinking plays an important role in resurfacing the tear film and expressing the meibum from the meibomian glands.15 The completeness of the blink is also equally important, as a partial blink will leave the inferior part of the cornea exposed to the environment, which would lead to greater severity of DED. The normal blink rate is 15 to 17 blinks per minute, while reading or using a digital device drops our blink rate to 4.5 blinks per minute.16

THE NEXT STEP

If our diagnostic testing shows normal results or improvements, but patients are still symptomatic for DED, we may need to consider comorbidities, such as conjunctival chalasis, blepharitis, allergic conjunctivitis, epithelial membrane dystrophy or Salzmann’s nodules, which all can mimic symptoms of DED.

Although DED can be present with any of these mimickers, additional treatments, such as lid scrubs (See “Defy Dry Eye,” p.20) and/or an ocular allergy medication, may be necessary.

Clinical experience matched with the diagnostic tools available in our repertoire help us make that diagnosis. Please keep these diagnostic tests in mind when you see your next DED suspect. OM

REFERENCES

  1. Farrand KF, Fridman M, Stillman IÖ, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017; 182: 90-98.
  2. Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012; 31: 472-478.
  3. Kim J. The use of vital dyes in corneal disease. Curr Opin Ophthalmol. 2000 11: 241-7.
  4. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea. 2006; 25: 900-7.
  5. Acera A, Rocha G, Vecino E, Lema I, Duran JA. Inflammatory markers in the tears of patients with ocular surface disease. Ophthalmic Res. 2008; 40: 315-21.
  6. Chotikavanich S, de Paiva C, Quan Li D, et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci. 2009; 50: 3203-09
  7. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci. 2006 Oct; 47: 4309-15.
  8. Sullivan BD, Crews LA, Sönmez B, et al. Clinical utility of objective tests for dry eye disease: variability over time and implications for clinical trials and disease management. Cornea. 2012;31: 1000-08.
  9. Wang CX, Liu YZ, Yuan J, Li BB, Zhou SY. Application of anterior segment optical coherence for measuring the tear meniscus height in the diagnosis of dry eye diseases. Zhonghua Yan Ke Za Zhi. 2009 Jul; 45: 616-20.
  10. Shen L, Suresh L, Lindemann M, et al. Novel autoantibodies in Sjögren’s syndrome. Clin Immunol. 2012; 145: 251-255.
  11. Arita R, Itoh K, Inoue K, Amano S. Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmol. 2008; 115: 911–915.
  12. Bron AJ, Benjamin L, Snibson GR. Meibomian gland disease. classification and grading of lid changes. Eye (Lond). 1991; 5 (Pt 4):395-411.
  13. Pflugfelder SC Tseng S Sanabria O, et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea. 1998; 17 :38–56.
  14. Finis D, Pischel N, Schrader S, Geerling G. Evaluation of lipid layer thickness measurement of the tear film as a diagnostic tool for meibomian gland dysfunction. Cornea. 2013; 32: 1549-53.
  15. Korb DR, Baron DF, Herman JP, et al. Tear film lipid layer thickness as a function of blinking. Cornea. 1994 Jul; 13: 354-9.
  16. Bentivoglio AR1, Bressman SB, Cassetta E, Carretta D, Tonali P, Albanese A. Analysis of blink rate patterns in normal subjects. Mov Disord. 1997 Nov;12: 1028-34.

PRODUCT LISTING

MMP-9 Tests
InflammaDry (Quidel)

Tear Osmolarity Tests
TearLab Osmolarity System (TearLab)
I-PEN Tear Osmolarity System (OCuSoft/I-Med)

Blink Rate Tests
BlinkCam (BlinkCAm)
iPEDA (Ophthalmic Resources)
LipiView (Johnson & Johnson Vision)

DX Equipment That Has Slit Biomicroscopy Algorithms
OSData (Ophthalmic Resources)

Corneal Topographers
Aladdin HW 3.0 (Topcon Medical Systems)
Atlas 9000 (Zeiss)
CA-200F Corneal Analyzer (Topcon Medical Systems)
CA-800 Corneal Analyzer (Topcon Medical Systems)
Cassini (EasyScan USA)
Galilei Dual Scheimpflug Analyzer (Ziemer Group)
Keratograph 5M (Oculus)
KR 7000P (Topcon Medical Systems)
OPD Scan III (Marco)
Orbscan III (Bausch + Lomb)
TMS-4N (AIT Industries)
Visionix VX110 Multi-Diagnostic Unit (AIT Industries)
VX120 Multi-Diagnostic Unit (AIT Industries)
Zeiss Atlas 992 (Zeiss)

Meibography
LipiScan (TearScience)
Meibox (Box Medical Solutions)

Meibomian Gland Expression Devices
Flexx Expressors (Ocusci)
iLUX (Tearfilm Innovations)
Mastrota Paddle (Medi Instruments)
Meibomian Expressor Paddle (Leduc)