Unlocking the role of

Dry eye diagnostic tools

Unlocking the role of inflammation in dry eye disease. Dermot McGrath reports

Although the pathogenesis of dry eye disease (DED) is multifactorial, with some aspects still not fully understood, ongoing research into the role that inflammation plays in the development and propagation of DED is opening compelling new avenues for the treatment of this complex disorder, according to Marc Labetoulle MD, PhD.

Speaking at the World Ophthalmology Congress 2020 Virtual, Prof Labetoulle, Hôpital Bicêtre, Paris, France, said that recent progress on the pathophysiology of DED has led to greater appreciation of the central role that inflammation plays in DED and its consequences for the eye.

“There are many consequences of ocular surface inflammation, including the loss of neuronal network in the cornea and infiltration of the lachrymal glands. It also participates in the induction / exacerbation of Meibomian gland disease (MGD) and triggers apoptosis of goblet cells. This inflammatory cascade can lead to aqueous deficient dry eye (ADDE) disease and/or evaporative dry eye (EDE) disease due to either lipidic or mucin instability,” he said.

The most obvious clinical consequence and direct marker of inflammation is epithelial damage on the cornea, noted Prof Labetoulle.

“This is what we have to assess in our everyday clinical practice. Assessing the epithelial damage is mandatory for the follow-up of patients and the efficacy of any anti-inflammatory treatment,” he said.

Corneal fluorescein staining (CFS), which is easy to perform, inexpensive, reproducible and which correlates with visual acuity and disease severity, is one of the most commonly used diagnostic tests for assessing the health of the cornea and DED, said Prof Labetoulle. Disease severity is typically assessed based on the Oxford classification, with a score greater than 3 (out of 5) indicating severe DED.

BIOMARKERS There is currently no single gold standard biomarker to diagnose and detect ocular surface inflammation, but ophthalmologists can already use different approaches, said Prof Labetoulle.

“In an ideal world, biomarkers could be our allies to defeat inflammation, In an ideal world, biomarkers could be our allies to defeat inflammation, not only by permitting us to detect the inflammatory process but also enabling us to determine the scale of severity... Marc Labetoulle MD, PhD

not only by permitting us to detect the inflammatory process but also enabling us to determine the scale of severity and to confirm the effectiveness of treatments, when to stop drug use, and to check the absence of relapse after their withdrawal,” he said.

Such biomarkers could ideally also help in the recognition of the pathogenic mechanisms underlying the inflammation, added Prof Labetoulle.

“They could help in distinguishing between ADDE and EDE or a combination of both, or to see if there is an associated allergy or other potential conditions that may participate in dry eye disease,” he said.

The most commonly used biomarker in clinical research is osmolarity, said Prof Labetoulle.

“Following on from the International Dry Eye Workshop (DEWS) reports, we know that hyperosmolarity can be both a cause and a consequence of DED,” he said.

The most frequently used machine to test osmolarity is TearLab (TearLab Corp.), which analyses tear fluid samples in a single test.

“The advantages are that the procedure is painless and quickly performed with less than two minutes for complete results. The quantitative results can be explained to patients and it has been shown that osmolarity provides a good combination of specificity and sensitivity when comparing patients against controls,” he said.

On the downside, Prof Labetoulle said that the reproducibility is not ideal and decreases in relation to ocular surface dryness.

“We typically need several measurements to increase reliability, it is quite expensive to use and, according to some studies, correlation with subjective and objective response to treatment is poor,” he said.

There are other specific devices to measure osmolarity such as the i-Pen (I-Med Pharma), said Prof Labetoulle, with complementary studies are needed to know if this device is comparable to TearLab.

Matrix metalloproteinase 9 (MMP-9) testing can also be used in clinical practice for assessing the inflammatory component when facing ocular surface dryness, said Prof Labetoulle.

“The test is fast, simple and painless with a positive/negative result, easy to communicate to the patient, and there is no real quantification. A study by Messmer in Ophthalmology 2016 showed that there is a correlation between MMP-9 positive test and subjective symptoms (as assessed by ocular surface disease index, OSDI), tear break-up time, Schirmer test results, conjunctival and corneal staining and number of obstructed Meibomian ducts and pathologic Meibomian gland secretion,” he said.

Other more technical options to assess DED include impression cytology for histological staining, noted Prof Labetoulle.

“The density in goblet cells is another good marker of chronic inflammation. It is also possible to look at the presence of inflammatory cells and it has been shown recently that in vivo confocal microscopy can give similar results. Conjunctival imprints can also be used to make a flow cytometric analysis of inflammatory markers in conjunctival epithelial cells of patients with dry eyes,” he said.

In the future, tear and serum biomarkers will probably play a greater role in the diagnosis and management of DED, concluded Prof Labetoulle.

“We are seeing a lot of interesting research in this area. The final step will probably be the use of microfluidic multipurpose machines, which will allow us to test multiple biomarkers from a very small sample of tears or serum,” he concluded.