Diagnosis

Get to the root cause of dry eye

Due to DED’s multifactorial nature, proper treatment depends on a precise diagnosis.

BY JAY S. PEPOSE, MD, PHD

Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface, comprised of a variable constellation of signs and symptoms. It is commonly characterized by elevated tear osmolarity (i.e., an elevated ratio of tear electrolytes to solvent), ocular surface inflammation, and dysfunction of one or more of the tear components. This results in tear film instability, damage to the ocular surface, discomfort (in most), and visual disturbances such as fluctuating vision.

A challenge with DED is that the signs and symptoms may poorly correlate at different times in the course of the disease. Many of the symptoms can be expressed as dryness, grittiness, foreign body sensation, burning, itching, tired eyes, light sensitivity, contact lens discomfort, or other terms. Later in the disease, some patients may have relative corneal denervation with characteristic ocular surface signs despite complaining of little or no symptoms.

For these reasons, diagnostic devices in the office setting play a critical role. They aid in the diagnosis of dry eye as well as differentiating its underlying pathogenesis and in monitoring the response to dry eye therapies.

The majority of DED is referred to as “evaporative dry eye,” meaning that there is blockage, shortening, or atrophy of the oil producing meibomian glands within the lids. These glands normally secrete oil that spreads across the outer tear layer, sealing in the tears. With a deficiency of the oil layer, tears evaporate at an accelerated rate, which is further exacerbated when the patient’s blink rate decreases, such as during computer use or due to incomplete blinks. The water component of the tears evaporates, which leads to ocular surface inflammation and damage.

Since the tears are the most powerful refracting element of the eye, unstable tear film may lead to fluctuating vision. A minority of these patients may have Sjögrens syndrome, an autoimmune disease in which their own immune cells attack and damage the lacrimal glands, resulting in a tear film insufficiency. Other patients have a mixed condition in which they experience both an increase in evaporation due to meibomian gland disease (MGD) and a decrease in production of the aqueous component of the tear film. Both of these mechanisms increase tear osmolarity, which is toxic to the corneal epithelium, leading to cell death and loss of corneal epithelial cell microvilli and their water-retaining glycocalyx.

Untreated dry eye may also lead to incorrect pre-surgical measurements, which depend upon uniform reflection from the ocular surface, and can produce poor visual outcomes.

Here, I describe the growing number of devices that aid in the diagnosis of dry eye disease.

Tear osmolarity

The point-of-care, CLIA-waved TearLab device can measure tear osmolarity. It collects 50 nanoliters of tears and analyzes osmolarity using lab-on-a-chip technology. This test should be used before instilling any drops or performing other tests that may alter the tear fluid. Abnormal results include an osmolarity value in either eye of 300 mosm/L or greater or an inter-eye difference of 8 mosm/L or greater.

Future testing on the same platform may allow quantifying biomarkers associated with T-cell inflammation.

LipiView and LipiScan

The LipiView II system with Dynamic Meibomian Imaging (TearScience) measures lipid layer thickness, evaluates blink dynamics, and directly images meibomian gland structures — all of which are essential in diagnosing evaporative dry eye. A smaller, lighter, portable meiboscopy unit, the LipiScan (TearScience), recently became available. It has a small footprint and works under normal lighting conditions. Diagnosed MGD can be treated using the LipiFlow system, which has been associated with improved patient scores on subjective dry eye questionnaires, lengthened tear break-up time, and improved meibomian gland scores in controlled studies compared to warm compresses, according to a 2012 Cornea article by Lane et al.

Keratograph 5M

The Keratograph 5M (Oculus) is a corneal topography device that can examine the meibomian glands, non-invasively determine tear break-up time and tear meniscus height, and evaluate characteristics of the tear lipid layer. One should not instill any drops prior to performing the test, as that could impact some of the test results, such as meniscus height and tear break-up time.

HD Analyzer

With the HD Analyzer unit (Visiometrics Division of Halma), users can assess an unstable tear film’s impact on vision. This device directly measures the retinal point spread function over time, taking images every 0.5 seconds while the technician instructs the patient not to blink. In a sense, this is similar to an automated tear break-up time, but does not require the instillation of any drops that can impact tear film characteristics, and it directly measures what the patient sees.

InflammaDry

Matrix metalloproteinases (MMP) are proteolytic enzymes produced by stressed epithelial cells on the ocular surface. MMP-9 in tears is a non-specific inflammatory marker. Its normal range is between 3 to 41 ng/ml. Elevated levels of MMP-9 in tears have been consistently noted in dry eye, as well as some other conditions associated with remodeling of the ocular surface.

InflammaDry (RPS) is a rapid, in-office test that detects elevated levels of MMP-9 protein in tears and can be performed in approximately 10 minutes via a colorimetric readout, much like the results of a pregnancy test. It is important not to instill any artificial tears or anesthetic or dilating or medication drops prior to performing this test. Also, keep in mind that even faint or broken red lines are considered positive.

Sjö

Approximately 10% to 15% of dry eye patients have Sjögren’s syndrome, which is a multisystem autoimmune disease that includes dry eye and dry mouth. It is important to make this diagnosis — not only to treat the dry eye, but also because these patients have an increased risk of developing lymphoma or complications involving the lungs, liver, or thyroid that may be minimized with earlier diagnosis, treatment, and monitoring.

In the past, the diagnosis of Sjögren’s syndrome was often delayed up to four years, partly because prior blood testing methods were less sensitive, particularly early in the disease. Recently a blood test, the Sjö panel (Bausch + Lomb), became available, which can be drawn in the office or sent to a local laboratory. This test picks up additional cases of Sjögren’s syndrome missed with older methods and also detects the disease earlier in its course, allowing for timely treatment, directed monitoring, and often a unifying diagnosis to a plethora of multi-organ symptomology.

Doctor’s Allergy

Ocular allergy or allergy treatment may accompany or exacerbate DED. Many allergy symptoms overlap with those of dry eye, creating a diagnostic dilemma.

Fortunately, a new FDA-approved in-office allergy skin testing system, Doctor’s Allergy formula (Bausch + Lomb), is available. It uses a plastic, skin-prick applicator to test the 58 most common ocular allergens from each region of the United States, obviating the need for needles or shots.

The test takes three minutes to perform and it takes 10 to 15 minutes for the skin reaction to develop, comparing each skin test response to a negative and positive control. Positive results can lead to appropriate treatment and often helps the clinician to differentiate between overlapping symptoms of dry eye, blepharitis, and ocular allergy. OP

Jay S. Pepose, MD, PhD, is a professor of Clinical Ophthalmology and Visual Sciences at Washington University School of Medicine in St. Louis, MO and founder and medical director of Pepose Vision Institute. He has a subspecialty in corneal and external diseases and refractive surgery.