Table 2

Summary of contributory DED criteria

Diagnostic testAdvantagesIssuesAssessment parametersSevere disease criteria
Refractory to standard disease treatments
Disease shows lack of therapeutic response
▸ Apparently a clinical indicator of severity.
▸ Might indicate ocular surface inflammation.
▸ May distinguish between mild and severe cases of DED.
▸ Might be used as an indication to initiate long term anti-inflammatory treatment (ie, topical cyclosporine).
▸ Definition of ‘standard treatment’ is critical.
▸ Not all the patients receive the same standard treatment.
▸ Refractoriness could be the consequence of inappropriate standard treatments.42
▸ Severity staging is needed.
▸ Discordance of symptoms and signs may be a pitfall.
▸ Long-term anti-inflammatory therapies, topical and systemic, may induce adverse events.
Not established
Confocal microscopy
May provide a non-invasive way to visualise high-resolution histologic-like patterns of the ocular surface structures.
▸ High resolution in vivo tissue examination.
▸ Minimally invasive.
▸ Useful for counting inflammatory cells and investigating corneal nerves.
▸ Provides overview of the whole ocular surface, including cornea, conjunctiva and limbus.
▸ Time-consuming.
▸ Expensive device not widely available.
▸ Needs an expert observer for specific diagnoses.
▸ Lack of scoring systems and quantitative methods.
▸ Nerve reconstruction software not available (images of narrow areas with limited value).
Not established in clinical setting
Objective measurement of the time course of high-order aberrations may constitute an instrument to evaluate and manage patients with DED.
▸ Non-invasive system.
▸ Gives rapid information about patient's visual problems.
▸ Useful for global definition of tear film conditions as a good indicator of tear film instability.
▸ Easily repeatable, can be used to monitor therapy efficacy.
▸ High sensitivity.
▸ Expensive instrument not easily available in all offices.
▸ Lack of specificity for the disease.
▸ Influenced by environmental conditions, quality of the last blink.
▸ Influenced by eye drops instillation.
▸ Unable to help characterise the disease.
▸ There is no objective way to extrapolate results and to predict real visual acuity of the patient.
Not well established
Inflammatory markers HLA-DR expression
HLA DR class II antigen is an immune marker abnormally expressed by epithelial cells in inflammatory conditions.
▸ Minimally invasive sample collection of conjunctival imprints.
▸ Expressed by the most important cell population of the conjunctiva, that is, epithelial cells.
▸ Large range of values; normal to severe dry eye.
▸ Highly expressed in inflammatory and immune diseases.
▸ Technique validated in several international multicentre trials with a central reading centre.
▸ Technique time-consuming; needs appropriate staff and expensive material
▸ Strict rules for collecting and sending specimens.
▸ Limited time before sample examination.
▸ Mainly designed for research and clinical trials.
Used as a biomarker in clinical trials, not established in clinical setting
Other inflammatory markers
MMP9, cytokines, proteomics and Luminex assays.
▸ Study disease pathogenesis at the molecular level.
▸ Minimal tear sample volumes needed.
▸ Possible multiple determinations for cytokines and MMPs.
▸ Precise/objective determination of molecular quantity.
▸ Easy collection: possible to analyse eluate from Schirmer's strips, cytology specimens, tear samples.
▸ Not definitely established correlation with severity of the disease.
▸ Not well defined role in specific dry eye pathogenic subgroups.
▸ Methods not yet very feasible for diagnostic purposes.49
▸ Labs not available in all clinical centres (useful only for smaller phase 2 or phase 3 trials).
Not well established.
Tear film instability is one of the core mechanisms of DED that can initiate, amplify and potentially change the character of DED over time.
▸ Global marker for DED.
▸ Non-invasive.
▸ Easy and rapid to perform.
▸ Accurate measurement is difficult (partly subjective).
▸ As yet no standardised procedure.
▸ Low specificity for subtypes.
▸ Poor correlation with other tests.
▸ Should be related to blinking status
Continuous gradingTBUT <3 s
  • These are clinical and biological markers or evaluations considered by the ODISSEY consensus panel to be indicative of DED, but are not yet sufficiently validated to establish diagnosis of severe DED.

  • DED, dry eye disease, HLA-DR, human leukocyte antigen-DR, MMP, matrix metalloproteinase, sec, second, TBUT, tear break-up time.