Summary of determinant DED criteria
| Diagnostic test | Advantages | Issues | Assessment parameters | Severe disease criteria |
|---|---|---|---|---|
| Conjunctival staining (including conjunctivochalasis/conjunctival folds) Several dyes may be used. Fluorescein is the most common, and is suitable for daily clinical practice. Lissamine Green is almost exclusively used in clinical trials. | ▸Staining is related to epithelial damage. ▸ Easy to perform. ▸ Good reproducibility (once examiner is fully trained). ▸ Already existing grading scales. ▸ Standard method is cost and time effective. | ▸ Epithelial damage is not correlated with subjective signs and improvement. ▸ Easy to overestimate or underestimate findings. ▸ Potential interexaminer variability. ▸ Many assessment scales available. ▸ Yellow filter may be expensive (and red filter is often not easily available). ▸ May need 2–3 min time window before correct assessment can be made. | Yes/no for presence of severe disease, as determined on any standardised scale (ie, Oxford Scheme14) | Yes, has severe disease as measured on scale |
| Schirmer Test Quantitative test for tear fluid availability. Measures maximal tear secretion capacity without anaesthesia. | ▸ Well established. ▸ Easy to use. ▸ Commonly accepted and available. ▸ Safe and efficient. ▸ Well tolerated (except with severe DED). | ▸ There is discussion regarding specificity and sensitivity. ▸ Dependent on corneo-conjunctival sensitivity, normal reflex regulations, uneven wetting of paper. ▸ Issues with reproducibility (ie, environmental factors). ▸ Issues with interpretation (ie, cut-off point). ▸ Issue with comparability (ie, variation of size, colour code, paper). ▸ Unknown effects of tear fluid composition (lipid layer alterations). | Continuous measurement—cut-off criteria for severe disease | <3 mm |
| Impaired visual function Blurred vision is part of the DEWS definition of dry eye. Any local change in tear film thickness has the potential to degrade retinal image quality. | ▸ Non-invasive technique. ▸ Information is easy to obtain from the patient. ▸ Can be self-administered by the patient ▸ Non-expensive. ▸ Can easily be part of standard patient work-up. ▸ Easily repeatable in controlled conditions. ▸ Can be used to monitor progression. | ▸ Subjective. ▸ External bias and confounding factors. ▸ Non-specific. ▸ Global tear film stability index. ▸ Cannot distinguish tear instability effects from cornea surface damage. | Yes/no | Yes |
| Filamentary keratitis Characterised by degenerated fragments of corneal epithelial cell and mucus firmly attached to the corneal surface. | ▸ Highly symptomatic. ▸ Good correlation with severity. ▸ Diagnosis is easy for general ophthalmologist. ▸ Small number of patients for clinical trials and brief course of treatment may allow a fast evaluation of results. | ▸ Non-specific for dry eye. ▸ Small number of patients with difficult recruitment. ▸ Medical treatment may not be sufficient. | Yes/no | Yes |
| Tear hyperosmolarity Thought to be a central mechanism of tissue damage in DED. | ▸ The most valuable single metric for diagnosis and disease management. ▸ A global marker for DED. ▸ Parallels disease severity. ▸ Responds to effective therapy. | ▸ Not yet widely available. ▸ Must distinguish between the subtypes of DED with other tests. ▸ Symptom improvement may lag behind tear osmolarity improvement. | Continuous measurement—cut-off criteria for severe disease | >328 mOsm/L |
| Impression cytology Conjunctival epithelium sampling method for use with immunocytology and histology | ▸ Minimally invasive. ▸ Well validated with published scoring systems. ▸ Goblet cell count as an objective marker. ▸ Specimens can be stored for a long period of time before processing. ▸ No major technical issue with standard cytological techniques. | ▸ Needs an external laboratory experienced in cytology and an observer trained in conjunctival pathologies. ▸ Assessment of squamous metaplasia only semiquantitative. ▸ Impression cytology provides only a small amount of possible information from biological specimens. | Nelson scale—cut-off criteria for severe disease48 | ≥Grade 3 |
| Blepharospasm Secondary to ocular irritation. | ▸ Good marker for severe DED. ▸ Has serious consequences for visual function. | ▸ Patients can have similar complaints as with DED. ▸ Patients do not associate visual fatigue with DED. | Yes/no | Yes |
| Meibomian gland disease or eyelid inflammation A condition of chronic inflammation of the eyelid. | ▸ Easy to diagnose (only if more severe/significant). ▸ Accessible to documentation. ▸ Standardised tools available.13 ▸ Few additional basic investigational tools required. | ▸ Subtle initial signs and stages, often not recognised. ▸ Issues with staging of the disease. ▸ Unknown effects to ocular surface disease (primary/secondary). ▸ Few additional facilitator investigational or diagnostic tools. | Yes/no to a severe degree | Yes |
These are clinical and biological markers or evaluations considered by the ODISSEY consensus panel as being sufficiently validated to establish diagnosis of severe DED.
DED, dry eye disease, DEWS, dry eye workshop, KCS, keratoconjunctivitis sicca, mOsm, milliosmole, TBUT, tear break-up time.