Challenging the conventional thinking in dry eye treatment

(Image Credit: AdobeStock/Alessandro Grandini)

Starting the treatment of dry eye disease early can be the most beneficial route, but nipping seemingly normal cases in the bud may be an art.

During this Ophthalmology Times Case-Based Roundtable, held during the American Society of Cataract and Refractive Surgery meeting in Boston, Richard Adler, MD, FACS, discussed numerous aspects of dry eye: definition, diagnostic testing, management, and asymptomatic cases to tease out the important considerations in these tricky cases. Adler is an assistant professor of ophthalmology at the Wilmer Eye Institute and director of ophthalmology at Belcara Health in Baltimore, Maryland.

Adler and the roundtable participants challenged conventional dry eye wisdom by actually discussing mostly normal eye examinations.

“Sometimes normal findings can be some of the most difficult findings to treat,” Adler said.

In this setting, he engaged the participants in a series of increasingly difficult diagnostic scenarios.

Ins and outs of case considerations

Case 1 was a 42-year-old asymptomatic woman who presented for her annual examination. She wore a monovision contact lens and worked on the computer 8 to 10 hours daily. Everything about the patient’s evaluation was normal except for the osmolarity value of 320 mOsm.

The Tear Film & Ocular Surface Society Dry Eye Workshop II defines dry eye as “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular surface symptoms in which tear film instability, hyperosmolarity, inflammation, and neurosensory abnormalities play etiologic roles.” Keeping this in mind, how should a clinician move forward?

In the patient under discussion with normal findings except for the osmolarity, Adler queried participants to see whether dry eye was diagnosable in this scenario.

Well, yes and no.

Although some thought it was nonsensical to diagnose dry eye disease, others noted that osmolarity is the key trigger of dry eye disease.

“Some participants believe clinicians are obligated to address the osmolarity in a patient who’s otherwise asymptomatic because of its trigger status,” Adler said.

Another tricky scenario was that of basically the same patient with no hyperosmolarity, normal physical examination findings except for some symptoms, and perfect tear film. Can this be dry eye?

The participants generally agreed that in the presence of a normal eye examination and no tear film abnormalities, a symptomatic patient can have dry eye. This consensus was based on a term in the dry eye definition: neurosensory abnormalities.

“In that case, the damage is not to the cornea but involved the nerves,” Adler explained. “The discussion centered on neuropathic pain and how it is associated with dry eye.”

The participants also discussed how inflammation can cause both hypersensitivity and hyposensitivity, leading to the conclusion that a diagnosis of dry eye is justified when considering inflammatory as the disease basis even without signs.

“The bottom line,” he stated, “is that the absence of signs is not a sign of absence.”

Case 2 was similar to case 1 with a slightly different twist. The patient had both a normal presentation and physical examination. However, inflammatory matrix metallopeptidase-9 (MMP-9) testing was positive.

Based on this, the discussion shifted to the consideration of dry eye diagnostics and whether they change dry eye disease management.

The participants realized as a group that the focus on diagnostic tests is exclusively on positive results. However, it is equally important to understand the implications of negative test results.

Interpretation can be difficult. When MMP-9 testing is positive, most practitioners are more likely to start an anti-inflammatory treatment, according to Adler. However, he noted that when testing is negative, inflammation can still be present because MMP-9 is just 1 inflammatory marker.

Most roundtable participants agreed that they would start anti-inflammatory treatment even if a test was negative.

In another scenario, testing was positive for inflammation and an anti-inflammatory regimen was started. One month later, when the testing is negative, is the next step stopping the treatment regimen? No one said they would.

The final consideration revolved around an initially negative MMP-9 test and treatment was started anyway. One month into treatment, the result was positive.

The bottom line is that if the MMP-9 test is positive, doctors are more likely to start an anti-inflammatory drug. If the result is negative, there seems to be no confidence that the patient does not need an anti-inflammatory.

“We realized that whether our tests are positive or negative, the possibility of dry eye must be considered,” he explained. “We need to consider the role of inflammation and that the greatest value of our diagnostic test is not actually in changing the disease management, but it’s in educating our patients and improving [adherence].”

The last case again considered the same scenario to demonstrate that sometimes the normal cases can be the most challenging.

In this scenario, the examination is normal with no positive diagnostic test. The question here concerns the obligation providers have to the asymptomatic patient who has risk factors. In this case, the patient is aged 42 years, wears contact lenses, and does computer work.

Most physicians are reluctant to say that all patients with dry eye should be screened. However, Adler pointed out that screening is a reality in clinical practice, ie, every patient undergoes measurement of the IOP whether or not they have glaucoma. The questions remain regarding establishing a baseline using the ocular surface disease index (OSDI), tear film breakup time, and Schirmer testing.

“Every patient in our practice who has dry eye at one time did not, and dry eye can develop in every patient in our practice who does not yet have it,” Adler explained.

In this last of the difficult patients, the OSDI was 25, and the Schirmer test was 5, indicating moderate to severe disease.

“Most of us would have missed it if patients were not screened based on risk factors alone,” he emphasized.

Treatment options

Most participants agreed that early treatment is best before the disease becomes severe.

The treatments include cyclosporine ophthalmic solution (Restasis; Allergan and Cequa; Sun Pharmaceutical Industries) and lifitegrast ophthalmic solution (Xiidra; Bausch & Lomb).

Varenicline solution (Tyrvaya Nasal Spray for Dry Eye; Oyster Point Pharma) is a newer drug that induces more rapid tear production than the other medications. The newest drugs are the anhydrous class of medicines that include perfluorohexyloctane ophthalmic solution (Miebo; Bausch & Lomb) and cyclosporine ophthalmic solution (Vevye 0.1%; Harrow).

Adler explained that Vevye, a semifluorinated alkane, has an inactive ingredient in the same category as Miebo and an active ingredient in the same category as Restasis.

“What sets Vevye apart is its tolerability, with 99.8% of patients in the pooled analysis having no or mild installation site pain,” he said.

“The roundtable discussion provided a greater appreciation of both the complexity of dry eye disease and the deceptive simplicity of a normal eye examination. We also have a greater appreciation for the complexity and the opportunity afforded by some of the newer therapeutic options. In a disease in which even a normal eye examination can be challenging, imagine now what would happen if you actually found something wrong,” he concluded.