November 2017

COVER FEATURE

Dry eye disease update
Diagnostics for dry eye


by Ellen Stodola EyeWorld Senior Staff Writer


Diffuse corneal staining in a patient with Sjögren’s syndrome
Source: Anat Galor, MD


Experts discuss some of the many testing options available for dry eye

Dry eye continues to be a problem that often goes untreated in many patients. However, there are a variety of diagnostics and testing options available for patients. Vatinee Bunya, MD, co-director of the Penn Dry Eye and Ocular Surface Center, Philadelphia, Anat Galor, MD, Miami VAMC, and Bascom Palmer Eye Institute, Miami, Christopher Rapuano, MD, director of the cornea service, Wills Eye Hospital, Philadelphia, and John Sheppard, MD, president, Virginia Eye Consultants, Norfolk, Virginia, discussed which diagnostics may be best for certain patients and some of the tests they utilize in their practices.

Diagnostic tests for all patients

There have been many advances in diagnostics and therapeutics, but Dr. Sheppard noted that some of the best information comes from a directed and complete history and physical exam. “We use an incredible array of diagnostics to further the suspicions that arise from dissecting the patient’s symptoms and carefully looking for the most important signs on the ocular surface that will best direct therapy,” he said. “Our goal is to make the right diagnosis the first time and give patients the best chance of achieving a significant improvement in vision and lifestyle with the least amount of trial and error.”
Dr. Sheppard said that he uses questionnaires in dry eye diagnosis, specifically the Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire and a modified Ocular Surface Disease Index (OSDI). The modified OSDI used at Virginia Eye Consultants has six additional questions that further pinpoint history of allergy or blepharitis.
Dr. Sheppard frequently uses osmolarity, MMP-9, and meibography testing, and all technicians at his practice are trained to do this.
Dr. Bunya said that she currently has all of her dry eye patients fill out the OSDI questionnaire at every visit. “This allows me to follow their symptoms in a more quantitative manner,” she said. “However, I also find it useful to take a detailed history and have patients describe factors such as what improves or worsens their symptoms and what activities are most limited by their dry eye disease.” In select patients, she will use additional testing such as meibography, MMP-9 testing, or LipiView (TearScience, Morrisville, North Carolina).
“All of my dry eye patients fill out an OSDI questionnaire at each visit, and I also perform a traditional ocular surface evaluation including tear breakup time (TBUT), ocular surface staining with fluorescein and lissamine green, and Schirmer’s testing,” Dr. Bunya said. “Depending on those results, I decide if additional testing is needed.”
Dr. Galor said that a comprehensive but quick and standardized way of assessment is important for dry eye, especially because there are so many subsets of dry eye. She will start with a standardized questionnaire. She then checks tear osmolarity and the presence of MMP-9 on the ocular surface with the InflammaDry (Quidel, San Diego).
Dr. Galor evaluates eyelid anatomy and laxity and uses a penlight to retroilluminate meibomian gland anatomy. She follows this with a slit lamp examination noting TBUT, staining, tear lake height and location, conjunctival chalasis, and eyelid margin features. She uses a combination of these tests to group individuals into four main categories: (1) inflammatory/aqueous tear deficiency, (2) evaporative deficiency/meibomian gland issues, (3) anatomical issues of the eyelids/conjunctiva, (4) nerve dysfunction.
There are other diagnostic tests available to quantify various aspects of tear film and ocular surface health, such as the LipiView, which quantifies lipid thickness, and the Pentacam (Oculus, Arlington, Washington). The Keratograph (Oculus) is another potential diagnostic that can highlight meibomian gland atrophy, non-invasively measure TBUT and tear meniscus height, and quantify bulbar hyperemia.
That said, Dr. Galor doesn’t routinely use these imaging devices as part of her dry eye workup.
Dr. Galor stressed that it isn’t always about what test to use. “You should look at your practice and flow, then figure out what to do that’s standardized,” she said.
Dr. Rapuano said it’s nice to first have a questionnaire, adding that he tries to use the OSDI, but it sometimes can be challenging to use this in a busy practice. He said the SPEED questionnaire is also helpful.
Dr. Rapuano mentioned the UNC Dry Eye Management Scale, which has a line that has a sad face on the left and a smiley face on the right, and patients put an X where they think their symptoms are.
In addition to questionnaires, Dr. Rapuano will use fluorescein staining and a slit lamp exam on every patient, as well as look at TBUT.
Typically, he’ll do lissamine green staining, which can pick up some of the earlier dry eye and ocular surface problems on the conjunctiva. On the first visit, he will often do a Schirmer’s test as well because if it’s really high or really low, this could be helpful.
Depending on the patient, he will also use osmolarity testing, but Dr. Rapuano noted that osmolarity can only be done on an eye that you haven’t done anything to, like checking pressure, putting in fluorescein, etc. Oftentimes, he is not able to do osmolarity on the patient’s first visit because by the time he sees the patient, too much has been done on the eye.

MMP-9 point-of-care testing

Dr. Bunya said that MMP-9 testing can potentially be useful in certain situations, such as evaluating asymptomatic patients prior to cataract or refractive surgery for subclinical dry eye disease, but she added that further studies are needed. “Also, if MMP-9 testing results are shown to be prognostic of results to different therapies, this would be clinically useful in guiding treatment,” she said. “However, more studies are needed to clarify the role of MMP-9 point-of-care testing in dry eye disease.” One caveat that is important to keep in mind when interpreting MMP-9 results, she added, is that this test can be elevated in other ocular conditions, such as infection and allergic conjunctivitis.
Dr. Rapuano thinks that InflammaDry MMP-9 testing may be helpful to find evidence of inflammation, although he noted that he does not routinely use it. He said that a new osmolarity test from TearLab (San Diego), the Discovery System, will include both osmolarity testing and two inflammatory markers, MMP-9 and IL-1Ra levels, in one test.

Meibography and diagnosing dry eye

“I think that meibography has a role in evaluating meibomian gland dysfunction and evaporative dry eye disease, and as more research is done regarding the interpretation and quantification of image findings, its clinical utility will increase,” Dr. Bunya said.
Sometimes it can be helpful in assessing a patient’s likelihood of responding to treatment. “I currently order meibography on patients who have moderate to severe dry eye disease to evaluate how much meibomian gland dropout is present,” she said. “If patients have a significant amount of meibomian gland dropout, I may recommend more aggressive therapies and will also counsel patients that they may only see a modest improvement with treatment.” In addition, meibography can provide information about the morphology of the glands.
Dr. Rapuano said that although he doesn’t currently use meibography technology, he thinks that there is great potential for its use as this can help the physician look at the meibomian glands and not just the pores.
Dr. Galor agreed that it is helpful for the surgeon to look at the meibomian glands and anatomy, either using retroillumination with a penlight or with more sophisticated imaging modalities.

Serologic tests for Sjögren’s

There are standard blood tests for Sjögren’s disease, Dr. Rapuano said, adding that the problem is that the tests are often negative if patients have early disease. Patients could have bad dry eye but no other rheumatologic symptoms and standard testing doesn’t point to Sjögren’s. However, the patient may develop more obvious rheumatologic symptoms years later, at which point the standard tests become positive.
The Sjö test (Bausch + Lomb, Bridgewater, New Jersey) is a blood test that was designed to identify Sjögren’s disease at a much earlier stage than standard testing. It was originally done in the office as a finger prick, Dr. Rapuano said. This was not very successful because many of the tests did not have sufficient quality or quantity. He added that today patients are sent to the lab for testing, and the test looks for 10–15 early markers for Sjögren’s. If one marker shows up, this could be suspicious, and additional positive markers could be very significant, at which point the patient may be referred to a rheumatologist. “If you send a patient to a rheumatologist with a positive Sjö test, this would be taken more seriously than symptoms of dry eye,” Dr. Rapuano said.
Dr. Galor said she is excited about these tests. “We know that the older Sjögren’s syndrome markers (SS-A and SS-B) become positive late in the disease, thus by the time individuals are diagnosed, the therapeutic window may have already passed. These markers may allow us to diagnose Sjögren’s syndrome earlier. However, they are not part of the current disease definition, and oftentimes, we don’t know how to fully interpret the results,” said Dr. Galor, adding that she will monitor these patients and depending on other comorbidities, send them to a rheumatologist.
Dr. Sheppard thinks the tests can have an important role for both the dry eye patient and the managing physician. Once a patient develops severe dry eye, the diagnosis of Sjögren’s becomes almost redundant to the eyecare professional, he said. Early diagnosis of Sjögren’s is extremely desirable, however, because of the numerous potentially severe systemic ramifications, and these patients are grateful to get early aggressive intervention from all of the specialists—ocular, dental, and rheumatologic. “It’s important to understand that these lab tests can guide us in recommending the best therapy,” Dr. Sheppard said.

Editors’ note: Dr. Bunya has financial interests with Bausch + Lomb. Dr. Rapuano has financial interests with TearLab. Dr. Sheppard has financial interests with TearLab, TearScience, Quidel, Allergan (Dublin, Ireland), Bausch + Lomb, Topcon (Oakland, New Jersey), and Novartis (Basel, Switzerland). Dr. Galor has no financial interests related to her comments.

Contact information

Bunya
: vatinee.bunya@uphs.upenn.edu
Galor: agalor@med.miami.edu
Rapuano: cjrapuano@willseye.org
Sheppard: jsheppard@vec2020.com

Diagnostics for dry eye Diagnostics for dry eye
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