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  • Clinical Update

    Consensus Report Simplifies Dry Eye Diagnosis

    By Victoria L. Wilcox, Contributing Writer, interviewing Ahmed Al-Ghoul, MD, MBA; Deepinder K. Dhaliwal, MD, LAC; Stephen Pflugfelder, MD; and Norihiko Yokoi, MD, PhD
    Cornea/External Disease

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    The complexity of dry eye disease (DED) and the growing influx of patients who have it make diagnosing this condition challenging and time-consuming.

    To simplify diagnosis, a group of ex­perts from around the world released a clinically oriented consensus definition of DED.1 They also offered practical ways to consistently diagnose DED and identify the pathophysiology behind individual cases. Moreover, no new equipment is required. As Deepinder K. Dhaliwal, MD, LAc, at the University of Pittsburgh School of Medicine, put it, “All that’s needed to diagnose dry eyes are a history, a slit lamp, and a fluores­cein strip.”

    The New Diagnostic Criteria

    Why new criteria were needed. In 2016, an international group of experts began discussing the need for a global definition of DED. Stephen Pflugfelder, MD, at Baylor College of Medicine in Houston, joined in the effort. He said that some of the prevailing diagnostic criteria, such as those from the Tear Film and Ocular Surface Society Dry Eye Workshop II (DEWS II),2 were clinically impractical.

    In addition, ophthalmologists in dif­ferent parts of the world defined DED differently, complicating international clinical trials. For example, DEWS II proposed two types of DED, aqueous deficient and evaporative, which were thought to occur on a spectrum.2 The Asia Dry Eye Society proposed a third type: decreased wettability dry eye.3 Patients with this type produce enough tears, but their tears break up quickly due to insufficient or abnormal mem­brane-associated mucin.

    The new definition. After four meet­ings, the experts issued their definition in a report published in 2020: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or defi­cient tear film causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation, and neurosensory abnormalities.”

    Notably, this definition revolves around tear film instability or deficiency, which clinicians can easily measure. In fact, the panelists deemed unstable tear film, when accompanied by ocular dis­comfort or impaired vision, sufficient to diagnose DED. They also recom­mended checking all dry eye patients for epitheliopathy, inflammation, and neurosensory issues.

    Key Symptoms and Signs

    Ocular discomfort. “In most cases, ocu­lar discomfort is displayed before DED is diagnosed, and it is critical for moni­toring the progression of the condition and response to treatments,” the panel wrote.1 Discomfort greatly affects the daily lives of dry eye patients, especially those who view electronic screens a lot, said panel member Norihiko Yokoi, MD, PhD, at Kyoto Prefectural University of Medicine in Japan. He explained that tear film breakup, friction during blink­ing, and lid margin problems such as meibomian gland dysfunction can all cause discomfort. Neurologic problems may also contribute.

    Pearls. Given the prevalence of DED, Dr. Pflugfelder recommends asking all patients whether they experience symp­toms of dry eye. And Dr. Dhaliwal asks patients: “What are the top three things that bother you about your eyes?”

    According to the consensus group, taking detailed notes of patients’ symptoms and their triggers may reveal the cause.1 For example, irritation that grows as the day goes on suggests DED, whereas pain that increases in the morning or the middle of the night may indicate recurrent corneal erosions or epithelial basement membrane dystro­phy, said Ahmed Al-Ghoul, MD, MBA, at the University of Calgary in Canada.

    Questionnaires. Giving patients a questionnaire can help complete the picture. Dr. Pflugfelder said that he often learns more about symptom severity from questionnaires than from what patients say. Dr. Al-Ghoul uses questionnaires to quantify patients’ condition at baseline and throughout treatment. Those data guide treatment decisions.

    The panel recommended several questionnaires, including one called Symptom Assessment in Dry Eye.1 Dr. Pflugfelder uses this visual an­alog scale in his practice. Its two items instruct the patient to mark a spot on a line corresponding to, first, the fre­quency of dryness and irritation, and, second, the severity of symptoms.

    Visual impairment. Unstable tear film can cause fluctuating visual im­pairment, which standard vision tests are not designed to detect. According to Dr. Pflugfelder, they test how well people see in high-contrast conditions, but reduced-contrast vision charts are better at detecting blurry vision in DED.

    To assess the visual impact of dry eye, Dr. Al-Ghoul deems the history crucial. Questionnaires, like the Ocular Surface Disease Index and the Standard Patient Evaluation of Eye Dryness, shed light on patients’ functional visual acuity, he said.

    Unstable tear film. Evaluation of tear film stability often starts with de­termining the fluorescein tear breakup time. Stained tears that break up within 1 or 2 seconds of the last blink suggest the patient has more severe dry eye and/or corneal disease than the typical dry eye patient, said Dr. Pflugfelder.

    Tear film breakup patterns. “Once it’s established that the patient has unstable tear film, there should be some attempt to identify the underly­ing problem,” Dr. Pflugfelder said. The problem could arise from either the lipid layer or the aqueous layer of the tear film or from the wettability of the corneal surface. Making this determina­tion can be facilitated by tear film–oriented diagnosis.3

    With this approach, Dr. Yokoi and colleagues used fluorescein staining to study how tear film breaks up. They found five essential breakup patterns that correspond to specific types of DED.4

    Area breaks and line breaks reflect lacrimal gland dysfunction, which results in aqueous tear deficiency and, generally, epithelial damage. Area breaks signify more severe disease than line breaks.

    Spot breaks and dimple breaks reflect decreased corneal wettability, perhaps due to a disrupted glycocalyx,3 whose glycoproteins help keep the ocular surface hydrophilic.5 Both of these patterns are characterized by short breakup times despite normal tear volume and no significant epithe­lial damage.4 Spot breaks suggest more severe DED, with nearly instant tear film breakup and a greater impact on patients’ lives.6

    Random breaks suggest a compromised secretory mucin and/or lipid layer. The latter points to mild evaporative dry eye, chiefly meibomian gland dysfunction. Like spot and dim­ple breaks, random breaks in DED are typically accompanied by short break­up times and no epithelial damage.

    Pearl. For proper diagnosis, Dr. Yokoi noted that special instructions must be followed. After wetting the fluo­rescein strip with two drops of saline or artificial tears, the tester should vigorously shake the strip to remove excess liquid before briefly touching the top of the strip to the lower lid margin. Then, the patient should blink several times before softly closing and briskly reopening the eyes.

    Other Factors to Assess

    Inflammation. “Inflammation is very important, especially in aqueous deficient dry eye,” said Dr. Yokoi. He explained that in this type of DED, often seen in Sjögren syndrome, in­flammation in the body can afflict the eyes as well. Speaking more generally, the consensus panel described how in­flammation can perpetuate the vicious cycle of chronic DED.1

    Dr. Pflugfelder noted that ocular inflammation often presents no overt signs. To check for inflammation, he uses the Quidel InflammaDry test, an immunoassay that flags high levels of matrix metalloproteinase 9 (MMP-9), which he considers one of the best bio­markers for inflammation in DED.

    While additional testing for dry eye patients, such as MMP-9 and meibo­mian gland imaging, can be helpful, said Dr. Dhaliwal, “its important that all eye care providers feel empowered to treat dry eye even if they don’t have these tools.”

    Ocular epitheliopathy. The panel noted that epitheliopathy, common in DED, can disrupt the tear film, impair vision, and increase eye pain.1 Dr. Pflugfelder said all dry eye patients should be checked for epitheliopathy. To do so, he uses fluorescein dye for the cornea and lissamine green for the con­junctiva. The effects of dryness on the conjunctiva, which supports the cor­nea, are often overlooked, he said. Yet, he explained, an unhealthy conjunctiva or a decrease of the conjunctiva’s mu­cus-making goblet cells can destabilize the tear film.

    Neurosensory abnormalities. Dr. Pflugfelder suspects neurosensory abnor­malities in patients who have high scores (60-100) on the visual analog questions despite normal tear breakup time or rapid tear breakup time with a normal appearing corneal epithelium and no corneal or conjunctival dye staining. Usually, he said, the exam reveals un­stable tear film without tissue damage, which might normally explain symp­toms such as pain or wind sensitivity. “It’s like their threshold for sensing pain and discomfort is reduced.”

    Surgery. Sometimes heightened sen­sitivity occurs after LASIK or other sur­gery, said Dr. Al-Ghoul. He considers neurosensory problems in postsurgical patients who report significant pain.

    Cornea or CNS? Abnormal pain in DED may result from sensitization of the corneal surface or from the central nervous system, noted Dr. Yokoi. To discern the cause, Dr. Dhaliwal instills a drop of proparacaine. If that relieves the burning or other symptoms, she can treat the ocular surface with a high likelihood of improving symptoms. She refers patients who are not helped by the anesthetic to either a pain man­agement specialist or a primary care provider, who can prescribe medication for central neuropathic pain.

    Regardless of the root cause, all patients with possible neurosensory abnormalities need prompt referral to a cornea specialist, said Dr. Al-Ghoul. Left untreated for too long, such abnor­malities continue to progress, making it considerably harder to manage these patients. Earlier treatment equals more successful treatment, he said.

    Treat the Right Target

    The panel recommends tear film–ori­ented therapy,3 which aims to stabilize the tear film by restoring components found to be lacking. For example, Dr. Yokoi treats severe aqueous deficiency with punctal plugs. For decreased wet­tability, Dr. Pflugfelder might prescribe cyclosporine, which boosts the number of conjunctival goblet cells, or vareni­cline to spur the release of goblet cell mucins.

    Controlling inflammation, whether over the long term or during disease flare-ups, is a must to prevent ocular damage and to rein in symptoms, wrote the panel.1 Dr. Dhaliwal prescribes an­ti-inflammatories for most of her DED patients, who tend to present with sig­nificant disease. Dr. Pflugfelder, on the other hand, saves anti-inflammatories for patients with significant symptoms, moderate-to-severe ocular surface dye staining, or high MMP-9 levels.

    Tear film–oriented therapy allows for a tailored approach to treatment, which is of value in a booming market of dry eye therapeutics, said Dr. Dhaliwal.

    Simple Methods for a Complex Problem

    Dr. Dhaliwal contends that getting to the bottom of dry eye need not be overwhelming. The consensus diag­nostic criteria, if applied consistently, can point the way to minimizing ocular damage, she said.

    Yet the disease can remain com­plex, said Dr. Al-Ghoul, and the time may come to dive in and approach the diagnosis of some patients in a more detailed manner. “If we make it too simple, we can end up missing things, so the question becomes, ‘When do we make it simple? And when do we go detailed?’”

    ___________________________

    1 Tsubota K et al. Int J Mol Sci. 2020;21(23):9271.

    2 Craig JP et al. Ocul Surf. 2017;15(4):802-812.

    3 Tsubota K et al. Eye Contact Lens. 2020;46(1):S2-S13.

    4 Yokoi N et al. Am J Ophthalmol. 2017;180:72-85.

    5 Uchino Y. Invest Opthalmol Vis Sci. 2018;59:DES157-DES162.

    6 Shigeyasu C et al. Diagnostics (Basel). 2020;10(9):711.

    ___________________________

    Dr. Al-Ghoul is clinical assistant professor of ophthalmology at the University of Calgary, Alberta, Canada. Relevant financial disclosures: None.

    Dr. Dhaliwal is a professor of ophthalmology at the University of Pittsburgh School of Medicine, Penn. Relevant financial disclosures: Oyster Point: C.

    Dr. Pflugfelder is professor and James and Margaret Elkins Chair in Ophthalmology at Baylor College of Medicine in Houston. Relevant financial disclosures: None.

    Dr. Yokoi is professor at Kyoto Prefectural University of Medicine, Japan. Relevant financial disclosures: None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Al-Ghoul Alcon: C; Allergan: C.

    Dr. Dhaliwal Allergan: C; Haag-Streit: C; Johnson and Johnson: C; Kowa Ameri­can: S; Lenz Therapeutics: C; Novartis: C; Ocular Therapeutix: C, L; Oyster Point: C; Staar Surgical: C; TearSolutions: C; Trefoil: C.

    Dr. Pflugfelder AbbVie: C; Dompé: C; Im­munEyez: O; Kala: C; Kowa: C; Senju: C.

    Dr. Yokoi Alcon: S; Otsuka: L; Rohto: C; Santen: L,C; Senju: L.

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