When old, new technologies converge for dry eye diagnosis

Reviewed by David B. Glasser, MD

Columbia, MD-Though several new tests and treatments for dry eye disease look promising, they may best be used in combination with older techniques, according to David B. Glasser, MD.

“There is a long list of things that have come to the forefront over the past few years,” said Dr. Glasser, assistant professor of ophthalmology, Johns Hopkins University School of Medicine, Columbia, MD, who specializes in treating the condition.

“Some of the tests are easy to do; some are hard; some are inexpensive, and some are expensive,” he explained. “How do we know we’re getting ‘real bang for the buck?’”

Old-school tools still work well, he added.

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“What you have in your office right now is enough to diagnose and manage patients with dry eye disease,” said Dr. Glasser, who is also in private practice, Columbia, MD.

Making the diagnosis

Making the diagnosis

Clinicians should start by taking a patient history or using a questionnaire, such as the Ocular Surface Disease Index (OSDI) or Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, Dr. Glasser said.

Staining the cornea and measuring tear film breakup time (TFBUT) with fluorescein and staining the conjunctiva with lissamine green or rose bengal can also provide valuable information. The slit lamp, keratometer, and Schirmer test all remain useful.

“No one should become too enamored of one test,” Dr. Glasser said. “A lot of it is experience, listening to the patient and looking at the results of a variety of tests.”

In a 2011 trial led by Michael A. Lemp, MD, clinical professor of ophthalmology at Georgetown University and George Washington University (Am J Ophthalmol. 2011;151:792), bilateral tear osmolarity appeared more accurate than TFBUT, corneal staining, conjunctival staining, Schirmer test, and meibomian gland grading.

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“That’s what people seem to have taken away from that study, and it’s been used to promote the usefulness of that test,” Dr. Glasser said. “It warrants a little closer look. Osmolarity was the best but it wasn’t that good as a stand-alone test.”

Osmolarity had only a sensitivity of 73% and a specificity of 92% at a cutoff of 312 mOsms/L. That means it missed more than one-quarter of dry eye cases. Lowering the cutoff would result in capturing more true positives, but would increase the false positives, whereas raising the cutoff would have the opposite effect, Dr. Glasser said.

“What this tells us, and the real value of the Lemp study, is there is no one test that’s going to tell you whether you have dry eye or not,” Dr. Glasser said. “You need to synthesize and analyze the data from two or three different inputs to understand the type and severity of dry eye disease.”

Specific test you should perform

Dr. Glasser noted he has not found a need in his practice for new imaging techniques to measure meibomian gland function.

“There are expensive instruments that you can use to measure the meibomian gland or you can just press on the eyelid and assess the quality of the meibum that is expressed,” he said.

Dr. Glasser does advocate testing for Sjögren’s syndrome, however. One study (Br J Ophthalmol. 2012;96:1498) showed that patients tended to have worse symptoms if their dry eye stemmed from Sjögren’s syndrome.

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One reason for testing patients for Sjögren’s is that the disease is associated with other systemic problems, he pointed out. In his practice, Dr. Glasser tests all patients with moderate-to-severe dry eye disease for Sjögren’s, using blood tests for antinuclear antibodies (ANA), rheumatoid factor (RF), and Sjogren antibodies SS-A (Ro) and SS-B (La).

Since Lyme disease is endemic in his area and can also cause dry eye disease, Dr. Glasser also asks patients if they remember a tick bite or large red lesion. He routinely tests for Lyme antibodies with Western blot follow-up when the test is positive.

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A relatively new, commercially available test (Sjö, Bausch + Lomb) uses an in-office, blood sample to detect seven biomarkers associated with Sjögren’s. They include ANA, RF, SS-A, SS-B, salivary protein 1 (SP-1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP). Two of these biomarkers-CA6 and SP-1-are more sensitive than Ro and La antibodies. Dr. Glasser noted he has not adopted this test because he also likes to check for Lyme disease.

Treatment efficacy

Treatment efficacy

Evidence for the efficacy of some of the new treatments is also sparse, Dr. Glasser said.

Standard treatments-such as artificial tears, hot compresses, and efforts to control the environment with humidifiers and avoiding fans and vents-are often effective treatments for dry eye disease. Punctum plugs and topical cyclosporine are frequently useful in patients with more severe disease or patients whose condition is not responding to initial treatment.

Dr. Glasser also recommends omega-3 fatty acid supplements to patients, he said, noting that they often need at least 2 g per day/month to get benefits.

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Recent studies challenging the effectiveness of omega-3 fatty acids for cardiovascular disease have influenced some of his patients, he said.

“I’ve seen a rash of folks who came in with increased dry eye symptoms, and it’s because they stopped taking omega-3s,” Dr. Glasser said.

Patients with meibomian gland disease (MGD) may benefit from two relatively new devices (Lipiflow, TearScience; MiBoFlo ThermoFlo, MiBo Medical Group). Both work by applying heat and pressure to the eyelid.

The Lipiflow device works by creating an internal/external lid sandwich and applying pressure and heat at 42.5° C. MiBoFlo is an external metal probe delivering 42.2° C with pressure applied by the operator.

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Dr. Glasser could not find any published studies of MiBoFlo, the less expensive of the two devices.

In several studies, Lipiflow showed improvement in TFBUT, corneal staining, conjunctival staining, OSDI, and meibomian gland grading, with improvement lasting several months.

These initial studies lacked control groups and participants were chosen based on lack of response to traditional therapy. Because of the variability in dry eye signs and symptoms over time, there was a significant potential for the improvement to represent regression towards the mean rather than true treatment effect. Nor was there any accounting for concomitant therapy.

“They didn’t really stand up to the rigorous standards for evidence-based medicine,” Dr. Glasser said.

Better Lipiflow results

However, in one randomized, controlled trial (Cornea. 2012;31:396), Lipiflow showed better results in meibomian gland scores, TFBUT, OSDI, SPEED, and corneal staining. The study lasted only 4 weeks, so it is not clear whether the device provides long-term benefits, he noted.

Though he does not own a Lipiflow device, Dr. Glasser sometimes refers patients with severe meibomian disease to other clinicians who do.

“In my experience, patients with mild-to-moderate meibomian disease get good results with hot compresses,” he said. “The water has to be really hot-not scalding, but really hot. Heat and pressure have to be maintained for at least a minute two to three times a day.”

An external compress cannot deliver both internal and external pressure like the Lipiflow device, but home tap water can be as hot as, or hotter, than the Lipiflow and MiBoFlo devices.

As an alternative for patients with significant MGD or rosacea, Dr. Glasser offers oral tetracycline, doxycycline, or minocycline.

“Patients respond to tetracycline-type drugs because they also reduce inflammatory mediators,” he said. However, the antibiotic can cause adverse events, such as disruption of the gut flora and sensitivity to light, he noted.

Intense pulsed light-used to treat skin conditions, such as rosacea-may also prove effective in MGD, Dr. Glasser said. In theory, the heat melts excessively thick meibomian secretions and creates superficial vascular thrombosis-preventing delivery of inflammatory mediators to the glands, he noted.

“But there hasn’t been any published evidence that’s what is happening,” Dr. Glasser said.

A couple of retrospective, single-center studies have shown positive results. In one 45-day randomized, controlled trial in 28 patients (Invest Ophthalmol Vis Sci. 2015;56:1965), treated patients showed improvement versus baseline and control in lipid layer grade, TFBUT, and symptoms as measured by SPEED, and a self-assessment of persistence.

However, there was no discernible effect of the treatment on tear evaporation rate, osmolarity, hyperemia, or tear meniscus height.

“I haven’t used it,” Dr. Glasser said. “I can’t comment on it except to say it’s interesting. Hopefully, we’ll see more studies with longer follow-ups to see how persistent is the treatment effect.”

What lies ahead

Researchers have also reported on a couple of other proposed treatments.

In intraductal probing, clinicians insert a probe through the meibomian gland orifices to release the meibum. One recent trial showed good results, but did not have a good control group, he noted.

In lid margin debridement/scaling, the objective is to open the pore either manually or with a device (BlephEx), which works like a “tiny low-powered drill,” Dr. Glasser said.

In a randomized, controlled trial of the manual approach, researchers reported improvements. “That holds some promise,” he said.

Another question clinicians must face is how to bill for newer procedures. Just because the FDA has cleared a device, or a test or procedure has a current procedural terminology code, does not mean carriers will cover it, he noted.

When there is no coverage, “patients are usually billed directly by the physician, but you have to look at your payer contracts,” Dr. Glasser said.

Traditional tests-such as vital dye staining, tear breakup time, and Schirmer testing-are typically bundled into the billing for an office visit.

“Personally, I find spending a little more time talking to patients and finding out what their symptoms are-the timing, the activities, and tasks that are affected-is very helpful,” he said.

Dr. Glasser added that using a variety of tests is helpful, letting the results guide the treatment.

Want more? Visit the Ocular Allergy Resource Center

David B. Glasser, MD

E: dbg@comcast.net

This article was adapted from Dr. Glasser’s presentation at Cornea Subspecialty Day during the 2015 meeting of the American Academy of Ophthalmology. Dr. Glasser has no financial interest in the subject matter.