Point of care tests in Dry Eye Disease

Penny A Asbell MD, FACS, MBA

Currently, when we talk about dry eye disease (DED), we typically start with therapy that is the same for all patients – artificial tears, then maybe plugs, topical anti-inflammatories etc. Is this the best approach?

Looking at another common problem, joint pain, the doctor would not treat osteoarthritis the same as rheumatoid arthritis; we all know that joint pain has different mechanisms of pathology and treatment is directed accordingly. It is time that our approach to DED got more specific, based on mechanisms, and point-of-care testing may help move us forward to this patient-centred approach.

NEED FOR BIOMARKERS IN DED

Current DED evaluation involving vital dye testing and Schirmer testing is well known to be variable and neither sensitive or reproducible; these tests make it hard to diagnose and determine efficacy of treatment. What we need is minimally invasive objective metrics. Biomarkers are defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic process, or pharmacologic responses to a therapeutic intervention”. (NIH Definitions Working Group. Biomarkers and surrogate endpoints in clinical research: definitions and conceptual model)

The DEWS report of 2007 defined dry eye as follows: “Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.”

Since then several in-office point-of-care tests have become available addressing key issues in DED.

TEAR OSMOLARITY

Hyperosmolar tears have long been associated with DED and considered a hallmark of it. Laboratory research has demonstrated that hyperosmolar solutions are injurious to surface cells and lead to an increase in the production of inflammatory markers. TearLab’s OcuSense measures tear osmolarity, indirectly through electrical impedance, with only nanolitres of tears. It is easy and fast to find the tear osmlarity of each eye. Subsequent peer-reviewed articles have been mixed on its role in diagnosing DED. A literature review published in 2015 supported by TearLab found 72 per cent positive, 21 per cent neutral and seven per cent negative. (Clin Ophthalmol. 2015 Nov 2;9:2039-47)

Unclear issues include: Is variability the key finding?; Is one test per eye enough?; And, does a normal reading rule out DED?

Review of peer-reviewed publications over the last two decades confirms the growing interest in DED and matches the growing body of literature highlighting that inflammation is a core mechanism for DED. The problem likely involves both innate and adaptive immune response, with a dysregulation of a balance in the immune response.

Clinical research work is investigating inflammatory markers on the ocular surface through impression cytology sampling of conjunctival surface and tear analysis of cytokines. Going forward, this work may allow for a better understanding of the mechanisms contributing to DED and open up new targets for pharmaceutical treatment and possible new point-of-care tests.

The point-of-care test for inflammation is InflammaDry®, which measures one inflammatory mediator, MMP-9, and gives a ‘yes’ or ‘no’ answer, similar to a pregnancy test. The tip is rubbed along the conjunctiva before placing any eye drops, then placed in a container for several minutes, and the coloured stripes are then evaluated: ‘pink’ means the concentration of MMP-9 is greater than 40ng/ml – considered the upper limits of normal. RPS, the manufacturer, feels that only 40-60 per cent of DED symptomatic patients have significant inflammation and that these patients will respond best to use of anti-inflammatory treatments.

IMAGING IN DED

Imaging is integral in most of ophthalmic care and a regular component for a glaucoma and retinal evaluation. Now, imaging of the ocular surface may add an additional dimension in understanding DED and perhaps help in differentiating aqueous deficit from evaporative DED. The Keratograph® from OCULUS images (without the use of any eye drops or vital dyes): non-invasive tear break-up time (NITBUT), tear meniscus height, redness score, and meibomian gland imaging (meimography). Other devices, including LipiView, give metrics of lipid thickness in addition to meimography.

THE FUTURE

Look for expanding opportunities for in-office testing in DED. Be sure to evaluate carefully data on repeatability (precision), accuracy (does the test give a true value?), sensitivity and specificity. Is the result clinically significant? Is the test responsive to treatment? Ongoing studies and future trials should help us all understand how best to use point-of-care tests in DED and continue to progress to personalised care for ocular surface disease, including DED.

Further references available on request

Prof Penny A Asbell is Professor of Ophthalmology, Director of Cornea and Refractive Services, Director of the Cornea Fellowship Programme, Department of Ophthalmology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, USA

Penny A Asbell: penny.asbell@mssm.edu