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Game-changing technology, objective testing en route to revolutionizing dry eye management
The trend is toward compact, comprehensive, easy-to-use in-office equipment.
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Because there is increased understanding and more targeted diagnostics and therapeutics, there is more to do for dry eye patients than simply prescribe artificial tears. The TFOS DEWS II report redefined dry eye as a multifactorial disease, “in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”
“Now we have very specific ways of evaluating these components. We can measure osmolarity, detect and measure inflammatory cytokines, visualize and analyze the structural changes of meibomian glands, assess tear volume and much more. We have now a scientific basis for our treatment, which also helps our patients understand what we are doing and why,” OSN Cornea/External Disease Board Member Marjan Farid, MD, said.
Evaluation, she said, begins with a questionnaire, an important tool that patients can fill out in the waiting room and that clues the specialist in to what the symptoms are and what the issues might be. Farid uses a modified version of the SPEED questionnaire, updated by the American Society of Cataract and Refractive Surgery Cornea Clinical Committee to include questions that specifically relate to patients who are about to undergo cataract or refractive surgery.
“Identifying patients with dry eye disease (DED) before surgery is crucial to the success of the procedure. Questionnaires are simple, straightforward identifiers for patients who have DED and do not necessarily bring it up with the doctor,” she said.
MGD, tear osmolarity, inflammation
Meibography has been a game changer in clinical practice. LipiView and LipiScan (Johnson & Johnson Vision) are pioneering technologies and invaluable tools for the understanding of meibomian gland dysfunction (MGD) by both the doctor and the patient.
“Patients can see how the loss, dilation or disorganization of their meibomian glands look like as compared with normal glands. When they see those structural changes and understand their disease, they are more compliant with the treatment we recommend,” Farid said.
The LipiView system can also assess blink rate and blink quality. Proper blinking allows the upper lid to come into contact with the lower lid, squeezes the meibomian gland and spreads lipids over the ocular surface.
“It is a great tool for patient education. They realize they are not blinking properly, become more aware of their blinking and can help themselves with blinking exercises,” Farid said.
Tear osmolarity testing also provides an evidence-based approach to dry eye. Tear hyperosmolarity has been recognized to play a crucial role in triggering the self-perpetuating cycle of inflammation in DED. Measuring osmolarity and pro-inflammatory cytokine levels in tears is now possible and provides a scientific basis for treatment.
“We can measure inflammatory markers such as MMP-9 and lysozyme, as well as IgE, which is an allergy marker. Some of these testing methods are not very practical to use in the clinical setting, but technology is evolving toward simple, one-step, hand-held devices that can test all these proteins very rapidly,” Farid said.
Tear volume, breakup time, clearance
Tear volume was traditionally evaluated with Schirmer test, which is simple to use but not entirely reliable due to potential reflexive tear production. Ultrahigh resolution anterior segment OCT imaging now offers a more objective and advanced way of assessing tear volume by measuring the tear meniscus height. It is particularly useful as a tool in patients with Sjögren’s syndrome and low tear volume, but for practical reasons, it is currently used more in research rather than clinical settings, Farid said.
Tear breakup time (TBUT) is an easy and effective method to measure evaporation and tear stability. The traditional test with fluorescein is inexpensive, specific and indicative of visual quality.
“Often these patients complain of fluctuating vision. If they say they start reading and after 5 minutes cannot read any more, this is very much correlated with their TBUT,” Farid said.
Fluorescein TBUT has been classified as “invasive” because fluorescein may alter the physiologic composition and volume of the tear film and the paper strip might induce reflex tearing, hence affecting TBUT value. Alternative noninvasive methods are now available, such as interferometry and imaging tools including the LipiView, the Tearscope (Keeler) and the Oculus Keratograph 5M.
Delayed tear clearance or tear turnover may lead to an abnormally high concentration of pro-inflammatory cytokines and chronic inflammation. Fluorescein clearance test is a good technique to asses tear clearance and diagnose duct occlusion or partial occlusion.
“By instillng fluorescein and putting a testing strip in the lower cul-de-sac, you can assess how quickly it clears from the ocular surface. It is also a good method to evaluate the need for punctal occlusion,” Farid said.
Fluorophotometry is also a good method to assess tear turnover, but it is not clinically practical and is mostly used in research settings.
Ocular surface damage, Sjögren’s syndrome and allergies
Dyes such as fluorescein, rose bengal and lissamine green are commonly used to detect damage to the ocular surface, which may be present in DED. Lissamine staining will pick up degenerated conjunctival epithelial cells, while fluorescein will help identifying micro-erosion of the cornea at a later stage.
“Patients undergo fluorescein staining of the cornea when they are at the moderate to severe stage of DED. It is very useful for disease staging because the corneal and conjunctival tissue take up the fluorescein when there is breakdown of the epithelial cells’ tight junctions,” Farid said.
Emerging technologies include confocal microscopy, which examines corneal cells in vivo and can detect early changes in the epithelial and stromal layers correlated with DED.
Sjögren’s syndrome can now be diagnosed earlier with the Sjö test (Bausch + Lomb), promptly addressing and possibly preventing complications. The test is performed in the office with a finger prick and the blood sample, collected on a Whatman card, is sent to a specialized laboratory.
“Some Sjögren’s patients have already been diagnosed by the rheumatologist when they come to our office, but sometimes we are the first physicians these patients see, and the responsibility of accurate diagnosis and treatment is on the ophthalmologist. We have to have a higher suspicion for patients with severe aqueous deficient dry eye disease although they may have concomitant MGD. Look for other dry symptoms, like a dry mouth, and team up with a rheumatologist to carry out further tests,” Farid said.
The Sjö test identifies the standard biomarkers for Sjögren’s syndrome (anti-Ro and anti-La), as well as three other markers (salivary protein 1, carbonic anhydrase 6 and parotid secretory protein) that are expressed earlier in the disease process.
“Last but not least, look for concomitant allergies because a lot of DED patients have concurrent allergies,” Farid said.
In-office allergy testing trays are now available with a number of specific antigens. They are applied directly to the patient’s skin, and reaction occurs within 10 to 15 minutes.
“These tests cut down on a long process of referral, laboratory testing and multiple visits for the patient,” Farid said.
Compact, comprehensive tools
More and increasingly sophisticated technology is involved in the emerging testing modalities for dry eye. Many of these new devices are used at first for research purposes because they are expensive and not practical in the clinical setting. However, the trend is toward easy-to-use, compact and comprehensive diagnostic equipment, and some manufacturers have already made significant steps in this direction.
The LacryDiag ocular surface analyzer (Quantel Medical) incorporates interferometry, meibography, noninvasive TBUT and tear meniscus measurement in one imaging device.
“This interesting technology underscores the advancements being made in tear analysis and consolidation of multiple diagnostic devices into one,” Farid said.
LacriScience is developing a versatile hand-held diagnostic instrument, the VersaPen, a portable laboratory that uses surface plasmon resonance technology to detect chemical markers, particularly antigens, in a tear sample.
“This small device can give us measures of osmolarity, inflammation and many other ophthalmic markers all at the same time in the office,” Farid said. “I am looking forward to having this new tool available. It will bring tremendous improvement to our clinical practice, making diagnosis and monitoring of DED patients streamlined and easy.” – by Michela Cimberle
- For more information:
- Marjan Farid, MD, can be reached at Gavin Herbert Eye Institute at the University of California, Irvine, 850 Health Sciences Road, Irvine, CA 92697; email: mfarid@uci.edu.
Disclosure: Farid reports she is a consultant for Johnson & Johnson Vision, Shire/Takeda, Allergan, Bio-Tissue, Kala, EyePoint Pharmaceuticals, CorneaGen and Eyevance Pharmaceuticals.