The tech’s role in dry eye diagnostic testing

November 21, 2014

Many of us who have been in practice for more than a decade can remember a time when there were few dry eye diagnostic tests on the market, and none that were very reliable. Doctors would diagnose patients based on symptoms and their slit-lamp examinations. Fortunately, several new diagnostic technologies have emerged in this space, making the diagnosis and classification of dry eye more accurate and efficient.

Many of us who have been in practice for more than a decade can remember a time when there were few dry eye diagnostic tests on the market, and none that were very reliable. Doctors would diagnose patients based on symptoms and their slit-lamp examinations. Fortunately, several new diagnostic technologies have emerged in this space, making the diagnosis and classification of dry eye more accurate and efficient.

We now know that about half of the American population has clinically significant dry eye, but only half of these dry eye patients have ocular surface complaints.In the other half of the population-the half without dry eye-half of those patients complain of symptoms that sound like dry eye but that are actually caused by other conditions. It is clear that symptoms on their own are a poor indicator of whether a person has dry eye. Now that we have a number of easy-to-use, point-of-care diagnostic tests validated by the peer-reviewed literature, we can obtain objective diagnoses and grade its severity. Practitioners and technicians together play an integral role in the utilization of these technologies.

Creating a dry eye protocol

At the Ophthalmic Consultants of Long Island, NY, we have implemented a number of diagnostic tests that have made treating the root cause of dry eye more efficient and effective than ever. Below we explain the purpose of these tests and describe how we integrate them into our practice.

TearLab Osmolarity Test

Hyperosmolarity is the core pathophysiological mechanism that causes tissue damage in dry eye. Normal tear osmolarity is between 290 to 295 mOsm per liter, and as that measurement increases, so does the likelihood of mild to moderate and then severe dry eye. The TearLab Osmolarity Test (TearLab) captures just 50 nanoliters of tears from the tear meniscus to test patients for dry eye disease. It is a portable test that automatically converts the tear fluid sample data into an osmolarity measurement and displays the reading on an LCD screen within 10 seconds of docking the handpiece containing the sample. TearLab won an international award in 2009 for the predictability of its test. As the disease gets worse, the tear osmolarity measurement increases along with the inter-eye variability. If there is a difference of greater than 8 mOsm per liter between the readings of the two eyes, that is a hallmark for dry eye disease.

InflammaDry

InflammaDry (RPS) is a rapid, point-of-care test to detect elevated levels of matrix metalloproteinase 9 (MMP-9), an inflammatory marker elevated in the tears of patients with suspected dry eye disease. The clinical signs of dry eye often do not correlate with patient complaints, and MMP-9 has been demonstrated to be a sensitive marker for dry eye-its elevation may precede the appearance of clinical signs. The technician takes 30 seconds to collect the tear fluid sample from the inferior palpebral conjunctiva during the initial patient work up, then assembles and activates the test. The test may be interpreted after 10 minutes.

 

Sjö

Dry eye is usually one of the earliest symptoms of Sjögren’s syndrome, the second most common-and often undiagnosed-autoimmune disease. The Sjö test (Nicox) is an advanced diagnostic panel that detects traditional biomarkers for Sjögren’s syndrome (SS-A, SS-B, ANA, RF), in addition to three novel proprietary biomarkers (SP-1, CA-6, PSP). Traditional biomarkers detect only advanced cases of Sjögren’s syndrome and have low specificity and predictability.2 The new biomarkers are important because they detect Sjögren’s syndrome in its early stages. They can do this because they are gland specific and have much improved predictability, specificity, and sensitivity.3 

Sjögren's requires an understanding beyond traditional symptoms

The technician performs the test by pricking the patient’s finger with a single-use retractable lancet and placing large drops of blood on a collection card. Many doctors with phlebotomists on staff choose to simply have a tube of blood drawn or send the patients to participating third-party labs to have the blood drawn. The collection card or tube is then sent to a central laboratory (Immco) for analysis via a prepaid FedEx envelope. The laboratory returns a serology report that confirms or rules out Sjögren’s syndrome. That information can be passed on to the patient and used to refer the patient to a rheumatologist, if necessary.

Unfortunately, patients with Sjögren’s syndrome can also suffer from dry mouth, fatigue, muscle weakness, and vaginal dryness, among a myriad of other possible symptoms and conditions. Even worse, they are at risk of developing lymphoma and Raynaud’s syndrome. Sjögren’s patients frequently have thyroid disease and gastrointestinal problems as well. If we can help these patients-who often present first to eyecare professionals due to their dry eye symptoms-we can impact their lives in a meaningful way.

LipiView

The LipiView Interferometer (TearScience) utilizes white light interferometry to measure the absolute thickness of the tear film lipid layer by analyzing approximately one billion data points per eye. LipiView also analyzes the characteristics of the completeness of the patient’s blink, as the frequency and completeness of blinking is now thought to play a role in meibomian gland disease. The technician administers the test by positioning the patient on the chin rest on the tabletop unit. The LipiView then records 32 frames per second in real time as the patient fixates on a target. The test results help us determine which patients can benefit from treating obstructed meibomian glands with pulsating thermal lid massage (LipiFlow, TearScience).

Keratograph 5M

The Keratograph 5M (Oculus) is a Placido-based corneal topographer, but there are also six ways in which it can be used to measure the tear film. First, we can use meibography to get a reproducible image 3D analysis of the meibomian glands. Second, we can perform an automated, reproducible, noninvasive tear film break-up time. Third, we can obtain an analysis of the viscosity of the tear film by tracking the speed, direction, and viscosity of the particulate matter in the tear film between blinks. Fourth, the R-scan (redness scan) can be used to objectively grade conjunctival redness by using image analysis to obtain a sclera-to-blood vessel ratio that results in automatic classification of the red eye as grade 0-4. The perilimbal area can be analyzed separately so that ciliary flush can be graded and followed in cases of uveitis. Fifth, we can automatically measure the height of, and perform image analysis on, the tear meniscus. Sixth, we can assess the thickness of the lipid layer of the tear film by analyzing the spectrum of colors that are visible as a thick, normal lipid layer will have more colors present.

 

Benefits of objective data

A key benefit of these new tests is that they allow us not only to make the correct diagnosis but also to track patients’ responses to treatment and compliance. For example, if a patient has an elevated tear osmolarity score of 386 and has been adhering to a treatment regimen for four to eight weeks, we are able to test the patient again and show that the tear osmolarity score of 317-while not yet normal-has gone down closer to the normal range in response to just the first few weeks of successful treatment. Americans understand and operate based on numbers; they always want their health-related numbers to go down, from their weight to their blood pressure to their cholesterol. Being able to communicate dry eye numbers to patients encourages compliance. Many of our dry eye therapies work, but they work slowly. As they show improvements, these diagnostic tests allow us to remind patients of where they began.

How to create a dry eye center

The learning curve

From a technician’s perspective, the time and training that it takes to confidently administer point-of-care diagnostic tests for dry eye is minimal. A technician can administer all of these tests, even meibography, if she feels comfortable everting the lids. Most technicians are able to confidently and comfortably administer each test after only a couple of tries. Conveniently, none of the diagnostic tests need the practitioner to be present, with the possible exception of the meibography test with the Keratograph 5M (if the technician is not comfortable with lid eversion). The technician simply needs orders from the practitioner. Most of the tests are point-of-care, yielding results within a matter of minutes (Sjö is a laboratory developed test, with results being returned one week after the sample collection card is sent to the laboratory). If technicians can test each patient with dry eye symptoms before the doctor enters the exam lane, it not only helps the doctor to make the proper diagnosis but also improves workflow. The doctor enters the exam lane only once per patient encounter and can focus his or her time on treatment.

Assess dry eye from a systemic standpoint

Administering diagnostic tests also allows technicians to be more involved in patient care. As they play a larger role in the dry eye workup, they can feel confident explaining tests and procedures to patients, which in turn make the patient feel more comfortable that all staff members involved in their care are knowledgeable and committed.

If we fail to correctly diagnose dry eye patients, they will continue to suffer and will get worse with time. We know that half of normal patients have complaints that sound like dry eye (but are due to another condition), and half of patients with dry eye have no or minimal symptoms. Since symptoms are so misleading, it is critical to have objective diagnostic tests at our disposal. Stated differently, we want our patients to be symptom-free and happy, but we can no longer diagnose dry eye entirely based on the presence or absence of symptoms. Thankfully, we no longer have to.

 

References

1. Tomlinson A. Epidemiology of dry eye disease. In:Asbell P, Lemp MA,eds. Dry Eye Disease: the Clinician’s Guide to Diagnosis and Treatment. New York, NY:Thieme; 2006:1-15.

2. Shen L, Suresh L, Lindemann M, et al. Novel autoantibodies in Sjögren’s syndrome. Clin Immunol. 2012 Dec;145(3):251-5.

3. Shen L, Suresh L, Lindemann M, et al. Novel autoantibiodies in Sjogren’s Syndrome. Clin Immunol. 2012;145:251-255.