Diagnostic Protocol

DEWSII Dry Eye Disease Definition leads to Simple Diagnostic Protocol

Validated Questionnaires:

There are typically 4 different symptom surveys used to provide a score of how a patient self-assesses their symptoms. These include:

• DEQ5*
• OSDI*
• Speed – Standardized Patient Evaluation of Eye Dryness
• CDEA

*recognized in DEWSII as a validated survey

Testing Rationale: What does each test measure

Osmolarity:

Tear osmolarity has been demonstrated to have the highest correlation to disease severity of clinical DED tests and has been frequently reported as the single best metric to diagnose and classify DED.

• Tear osmolarity, an important biomarker of ocular surface, is a measure of the solute content of the tear film. Abnormal osmolarity indicates a breakdown of the homeostatic mechanism resulting in an unhealthy tear film, which can potentially damage the ocular surface and cornea.
  • Osmolarity > 300 mOsm/L and/or an inter-eye difference of greater than 8 mOsm/L indicates abnormal/elevated osmolarity and unstable tear film. 
  • A scale is used to grade the disease severity:
    • 300-320 mOsm/L-Mild DE
    • 320-340 mOsm/L-Moderate DE
    • >340 mOsm/L-Severe DE
  • There is greater inter-eye variability of osmolarity in DED than in normal patients.
  • The inter-eye variability has been shown to substantially reduce over time with successful treatment of DED.

Test both eyes to uncover abnormal osmolarity and determine severity.

Inflammation of the Ocular Surface:

According to the 2017 TFOS DEWS II Report, dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.

Inflammation is a recognized component of the pathophysiological mechanism of DED [4] and has been proposed to offer a stable indicator of DED severity. The matrix metalloproteinases (MMPs) are one of many classes of proteases secreted into the tears in DED [174,345–347]. The levels of MMPs reflect the loss of ocular surface barrier function, since MMPs can destroy tight junctions in the ocular surface epithelium. MMPs are not specific to the source of inflammation.

The lack of correlation between clinical signs and symptoms of dry eye disease makes diagnosing and treating patients a challenge. Often times, inflammation is present before the clinical signs of dry eye.

Tear Film Break-Up Time:

• TBUT, an evaluation of tear film stability, is the interval of time that elapses between a complete blink and the appearance of the first break in the tear film. This test can be performed by using fluorescein (FBUT) or without it, otherwise known as non-invasive breakup time (NIBUT).
  • FBUT reference value for DED diagnosis range from a cut-off time of less than 10s, to less than 5 s when a small, more controlled volume of fluorescein is used.
    • Drawbacks:
      • Sensitivity and Specificity in SS patients has been reported to be 72.2% and 61.6% respectively
      • Mild and moderate DED patient represent with broad ranges of FBUT values
      • FBUT measurement it is dependent on subjective assessment of the observer
  • NIBUT involves the observation of placido disk images that are reflected from the anterior ocular surface with many of the currently marketed corneal topography systems.
  • NIBUT cut-off value of less than or equal to 10s is thought to be indicative of DED, with the absolute values reported to be longer.
    • Sensitivity and Specificity, depending on the specific technique used, has been reported 82-84% and 76-94% respectively.

Ocular Surface Assessment:

• Punctate staining of the ocular surface is a feature of many ocular diseases and instilled dyes are extensively used in the diagnosis and management of DED.
  • Sodium fluorescein, rose bengal and lissamine green are commonly used.
• Depending on the dye used, different cell damage can be identified:
  • Sodium fluorescein: disruption in superficial cell tight junctions or defective glycocalyx.
  • Rose bengal: unprotected cells by mucin or glycocalyx, or dead/degenerated cells.
  • Lissamine green: only cells with damaged membrane.
• Both corneal and conjunctival staining have been shown to be informative markers of disease severity in the severe DED, however, staining of the ocular surface in mild/moderate DED has shown poor correlation to disease severity.

Tear Meniscus Height:

• It is the most direct approach to study the tear film volume, with good accuracy and correlations with other DED tests.
• Ranges: TMH less than 0.25 mm is suggestive of DED.
• Drawbacks and limitations:
  • When performed under slit-lamp:
    • Poor inter-visit repeatability
    • Operator-dependent
  • Influenced by:
  • Time after blink
  • Measurement locus
  • Time of day
  • Environment: Temperature, Humidity, Air speed, Illumination
• Digital Meniscometry: exhibits good reproducibility and good agreement with other methods of measure.

Meibography:

• It allows the observation of the silhouette of the meibomian gland morphological structure, such as the shortening, the distortion and/or the dropout of meibomian glands.
• Meiboscore in combination with symptoms and lid margin abnormalities demonstrated a sensitivity of 84.9% and specificity of 96.7% for the diagnosis of MGD.
  • Different gland scoring systems are available today to clinicians.