Here’s the scenario: Your patient presents with complaints of irritation, redness and a stinging, burning or scratchy sensation in her eyes. Maybe she also complains about sensitivity to light, blurred vision or trouble wearing contact lenses.

Are you looking at a mild case of dry eye disease (DED), in which case you prescribe artificial tears and send her on her way? Or could it be something deeper, more complex, that requires additional detective work and more substantial treatment?

The answer is critical, as incorrectly diagnosed DED doesn’t just affect quality of life, but it also can hinder the success of cataract, refractive and other eye surgeries.

Perhaps no other eye condition is less straightforward to fully identify and treat than DED, which afflicts some 30 million people in the U.S. (according to a 2014 American Jounral of Ophthalmology paper by Paulsen AJ et al). The challenge lies in the fact that DED is just one of many ocular surface diseases (OSD) and other underlying conditions that can either give rise to or even mimic DED.

“From a diagnostic standpoint, cataracts are much easier than OSD, which is contradictory to the way people have always traditionally thought of DED — as something boring and mundane,” says Christopher E. Starr, MD, FACS, an ophthalmologist at Weill Cornell Medicine Ophthalmology in New York City. “Many of our patients do present with symptoms of dry eye, but very few have just one OSD. And each requires its own diagnosis and targeted treatment.”

“We used to think of ‘underlying conditions’ primarily as systemic conditions that affect the eye: inflammatory diseases, autoimmune disorders, Sjögren’s disease, rheumatoid arthritis, lupus, sarcoidosis, things of that sort,” agrees Darrell E. White, MD, founder of SkyVision Centers in Westlake, Ohio, a Dry Eye Center of Excellence. “But there are localized underlying conditions that affect the quality or quantity of the tears. They say all politics is local. Not all dry eye is local, but most dry eye is, in some way, shape or form, local.”

Conditions and diseases that can cause DED include allergies, infections, meibomian gland dysfunction (MGD), blepharitis, conjunctivochalasis, pterygia, map-dot-fingerprint dystrophy and demodex mites. Other conditions can mimic dry eye symptoms, including droopy eyelids and superior limbic keratoconjunctivitis (SLK). In all these cases, simply targeting DED without addressing those other conditions is not likely to be effective.

And while DED cannot be cured, it can be successfully treated with a number of effective therapies, ranging from artificial tears to minor in-office procedures.

PATIENT HISTORY

The importance of starting with a comprehensive patient history is difficult to overstate. History and symptom surveys can illuminate many potential causative factors in DED; in many cases they can even obviate the need for some tests

“There are a number of things that we don’t go through often enough. For example, a variety of medications and environmental factors can trigger DED,” says Preeya K. Gupta, MD, associate professor of ophthalmology at Duke University School of Medicine in Durham, N.C.

An in-depth history, she says, can help identify these and other more likely suspects or accomplices responsible for any given case of DED. Conditions like floppy eyelid syndrome and SLK can “masquerade” as DED, causing symptoms like the foreign-body sensation and light sensitivity.

“But unless you look under the upper lid or ask the patient about it, you will miss these alternate diagnoses, which are treated differently than DED,” says Dr. Gupta.

In addition, the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, the Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire 5 (DEQ-5), and McMonnies dry eye questionnaire are all also used to screen patients for DED presence and severity.

Beyond screening questionnaires and surveys, several traditional and innovative tests can help physicians quickly and accurately narrow the causes of DED.

TEAR OSMOLARITY AND MMP-9 TESTS

Manufactured by TearLab and Quidel, respectively, tear osmolarity and MMP-9 (InflammaDry) measurements are first-line, in-office tests that provide objective information on the presence of factors, particularly inflammation, that influence the development of DED.

InflammaDry is a qualitative test that requires sufficient tear volume to acquire a sample. “And then it’s a pink line or no line,” says Dr. Gupta rather than a number readout. Dr. Gupta added that she would like future iterations of this test to provide more quantitative measurements to track patients over time and assess their response to therapy.

Another consideration with MMP-9 is that it is nonspecific and can be elevated in other inflammatory conditions of the eye, including allergies or other conditions affecting the ocular surface.

“When the InflammaDry test strip is dark red it implies substantial inflammation, virtually guaranteeing OSD. It could be pterygia, it could be conjunctivochalasis, it could be allergy, it could be infection, MGD, blepharitis, EBMD [epithelial basement membrane dystrophy] or others,” explains Dr. Starr.

Similarly, the TearLab osmolarity test is a qualitative, nonspecific test that must be interpreted with care, says Dr. White. “Tear osmolarity is either high or low, and either shows a degree of symmetry between the eyes or it does not. None of that is positive or negative. The meaning is different given the different settings,” he says, noting that a “relatively low tear osmolarity” doesn’t necessarily mean the patient does not have DED.

SLIT LAMP TESTS

Three long-standing tests used to detect and track down the causes of dry eye and other OSDs rely on the slit lamp combined with other tools. These tests are corneal and conjunctival staining, tear breakup time (TBUT) and meibum consistency.

• Corneal and conjunctival staining. Performed with fluorescein and/or lissamine (green), this is a traditional and inexpensive test but also an effective and reliable way to assess the health of the ocular surface, including the quality of the tear film (Figure 1). Subtle corneal pathology, such as anterior basement membrane dystrophy (Figure 2), can also be identified with fluorescein, in addition to punctate staining of the cornea and conjunctiva.

  

  

• TBUT. Also traditionally performed with the slit lamp, TBUT tests are extremely important, particularly in evaporative DED, which is the most common subtype and usually results from either a lack of lipid or meibum, or poor quality meibum, in the tear film. While most clinicians still use the slit lamp, many are also turning to complementary devices like Visiometrics’ HD Analyzer or the Oculus Keratograph 5M, which do not require dye and can be operated by ophthalmic technicians. “[TBUT] is very objective and reproducible. In fact, when you look at the 2017 Tear Film and Ocular Surface Society DEWS II report diagnostic algorithm, non-invasive tear breakup time was the recommended first-line test. The tear osmolarity test and the non-invasive tear breakup time, in addition to corneal staining, were the key diagnostic steps in their algorithm,” says Dr. Starr.
• Meibum consistency. Assessing meibum consistency is a matter of using the slit lamp to inspect the quality of the oil, which should flow like olive oil. Meibum that looks like toothpaste is abnormal. “It should be a fundamental part of everybody’s ocular surface exam,” Dr. Starr says. “It is easy to do, it’s free and it is fast.”

DYNAMIC MEIBOMIAN GLAND IMAGING

Meibography is among the most recent tools for dry eye diagnosis. Performed with the HD Analyzer (Visiometrics), Keratograph (Oculus), ICP MGD (Mibo Medical) and LipiView Interferometer (Johnson & Johnson Vision), meibography uses high-definition imaging to look for gland atrophy.

“A patient with severe atrophy is going to require multiple therapies and more intervention than a patient who doesn’t have any atrophy,” says Dr. Gupta. She describes meibography as an “excellent tool, especially if you’re taking care of dry eye patients regularly. There really isn’t a different tool that clinicians have to assess atrophy of the meibomian glands.”

Dr. White also has high regard for meibography. “Technology that allows you to show your patient what you’re discussing is going to be very impactful,” he says.

KERATOMETRY

While not routinely employed by most general ophthalmology practices, keratometry is used by eye surgeons prior to measuring tear film quality and helps inform surgical plans prior to cataract and refractive procedures. Dry eye and other OSDs can dramatically impact the results of these procedures.

“That’s where devices like the Marco OPD III and virtually any other topography unit will give important data on the health of the pre-corneal tear film,” Dr. Starr says. “Any dry spots, irregularities or lack of consistency in the measurements will present a much higher chance of suboptimal outcomes. The tears and ocular surface are critically important to refractive outcomes.”

NOT EVERY TEST REQUIRED UNDER EVERY CIRCUMSTANCE

While the newer tests are making their mark on dry eye diagnosis, they’re not yet being adopted by all practices, in part because of the expense tied to them for some patients.

“For example, Tear Lab, osmolarity, and MMP-9 are point-of-care tests, but the main issue … is that Medicare and private insurers may not cover all of them,” says Dr. Gupta.

Fortunately, longstanding basic tests like fluorescein and lissamine green staining are often sufficient to make a confident diagnosis, and only the most resistant cases will demand further investigation, she says.

As a dry eye specialist who operates a Dry Eye Center of Excellence, Dr. White sees mostly patients who have been unable to find satisfactory relief from their condition even after multiple attempts and “second” opinions have failed.

“If you’re a dry eye specialist like myself, we’re often the seventh opinion because it can be very challenging to get these people feeling well. It’s a question of what information do I need at that particular stage with that particular patient,” he says.

DESPITE CHALLENGES, THERE’S CAUSE FOR OPTIMISM

To be sure, obtaining a full diagnosis and treatment of DED remains challenging, and Dr. White believes that “parallel development” of new diagnostics and new treatments is necessary to bring about further progress.

“There’s the ongoing, everlasting, universal tension between the ability to diagnose and the ability to treat,” he says. “If you don’t have the ability to treat, there’s little need to diagnose. If you have the ability to treat, but you don’t have any way to precisely diagnose, then you’re faced with a case of ‘when you have a hammer, everything looks like a nail.’”

Still, there’s reason to celebrate. Dr. Starr describes a “revolutionary improvement” in diagnostic capabilities over the past decade that he credits to the original Tear Film and Ocular Surface Society DEWS report of 2007. “It is an extraordinary time to be doing this, because OSD and DED diagnosis and treatment have never been better,” he says.

“It’s incredible what we can do with the most basic tools at our disposal — a slit lamp, a little bit of fluorescein dye and a good history,” agrees Dr. White. “But the newer technology now allows us to double down on what we’re supposed to be doing all the time — not only making people healthier, but also helping them see better.” OM