DEWS report is comprehensive, but questions remain, experts say

Clinicians are well aware that dry eye disease is multifactorial and can be difficult to diagnose and manage. The challenge remains to develop treatment strategies that are not overly complicated for patients, according to the recently published Tear Film & Ocular Surface Society’s International Dry Eye Workshop Report.

The workshop is a result of a 2-year effort involving 150 experts from 23 countries working on 12 subcommittees.

Since the release of the first TFOS Dry Eye Workshop (DEWS) report in 2007, the number of publications relating to dry eye has almost doubled, TFOS DEWS II stated. As a result, the current report has grown to 380 pages, from 140 pages in 2007.

The objective was for the document to provide an “encyclopedia” or reference material for all things dry eye-related, Kelly K. Nichols, OD, MPH, PhD, FAAO, chair of the Definition and Classification Subcommittee, said in an interview with Primary Care Optometry News.

“With the evidence-based approach, you don’t speculate; you report what’s been done to date,” she said.

“It is evidence-based. There’s no bias or company angle. This is the state-of-the-art management therapy available at this time,” Lyndon Jones, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE, FBCLA, who sits on the steering committee and the Diagnostic Methodology and Management and Therapy Subcommittees, told PCON.

Revised definition

TFOS DEWS II revises the definition of dry eye:

“Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”

The addition of “loss of homeostasis” is significant, according to Nichols.

“If your tears aren’t normal and creating an environment that isn’t in equilibrium on the front of your eye, that will stimulate other negative processes throughout the eye,” she said.

“Homeostasis and ‘restored homeostasis’ is an important message, because you want your patient to feel better, but, ultimately, you’re trying to create a healthier tear film,” Leslie O’Dell, OD, FAAO, who served on the Public Awareness and Education Subcommittee and is a PCON Editorial Board member, said in an interview.

Scott E. Schachter, OD, who specializes in dry eye and ocular surface health at his practice in Pismo Beach, Calif., appreciates the recognition of the goal of returning homeostasis.

“There is a balance within the lacrimal function unit, and if you get a disruption in any part of those components, a patient can fall into a vicious cycle, and you have to interrupt that when you treat it,” he said.

In brainstorming on the new definition, Nichols noted that the committee wanted it to be simple and broad, but needed to narrow it down to be most effective.

They included terms more related to etiology, such as inflammation, osmolarity and the emerging concept of neuro-involvement, she said, which helps optometrists rule out conditions not related to dry eye.

Schachter also supports the recognition of patients with neuropathic pain, who are often frustrated and who can be frustrating to the optometrist.

“You look at them, and they look normal,” he said. “These patients spend a lot of time in your office and they will follow your recommendations to a ‘T’ but it doesn’t help ... something else is going on in the neurosensory system.”

“You can put [artificial] tears back [into the eye], but still the nerves are broken and damaged, sending abnormal signals, and this is what we call neuropathic pain,” Carlos Belmonte, MD, PhD, steering committee member and Pain and Sensation Subcommittee co-chair, told PCON. “It is extremely disabling and very difficult to sustain and treat. It is very limiting to be in this discomfort all day long. Patients cannot open their eyes properly; they cannot read or watch TV; it is very disturbing.”

At this point, the problem is no longer one for the optometrist or ophthalmologist, but for a neurologist or pain specialist, Belmonte said.

If a patient is complaining of continuous dry eye sensation pain, Belmonte suggests using a drop of local anesthetic. If the pain disappears, the origin is peripheral, at the level of the ocular surface, he said. If the pain is neuropathic due to malfunction at upper levels of the nervous system, it will persist even if you silence the signals that normally activate it.

“It is a very clear criterion to determine if the pain is due to the abnormal function of the nerves, if it is central neuropathic pain,” he said.

Diagnostics

The Diagnostic Methodology Subcommittee determined the most efficacious set of testing for diagnosing and monitoring dry eye disease (DED) based on the revised definition.

In dissecting the available peer-reviewed, published research on the frequency of dry eye, one challenge of the subcommittees was the lack of standardized diagnostic criteria for dry eye, according to Fiona Stapleton, MCOptom, PhD, DipCLP, FAAO, FBCLA, TFOS DEWS II steering committee member and professor and head of the School of Optometry and Vision Science at University of New South Wales in Sydney, Australia.

“The diagnostic criteria have varied among studies, so the disease prevalence has varied widely among studies,” Stapleton told PCON. “For example, studies that have diagnosed dry eye on the basis of clinical signs, like fluorescein staining of over grade 1 and tear break-up time less than 10 seconds, often report a prevalence of disease two to three times higher than those studies using report of symptoms of dryness and discomfort.”

The traditional approach to dry eye classification requires DED subjects to satisfy all criteria within a series of sensitive thresholds, such as Ocular Surface Disease Index (OSDI), Schirmer’s testing, tear break-up time and positive staining, according to the report.

“While this approach can produce strikingly high sensitivities and specificities of the diagnostic methods under evaluation ... this approach excludes many DED patients, as signs and symptoms are uncorrelated across the broad population and do not move in synchrony. For instance, it is very common to encounter a patient with a high level of symptoms and yet a lack of evidence of staining,” according to the report.

The committee recommended administering a validated questionnaire at the beginning of the patient interaction. The OSDI is recommended due to its popularity and establishment in the field, and the Dry Eye Questionnaire-5 (DEQ-5) is recommended for its “discriminative ability” and the fact that it is has only five questions.

“If you’re not asking about dry eye symptoms or using a dry eye survey, it’s a good time to start, because you will find more patients,” Nichols said.

“Questionnaires are helpful, but, overall, we know that many eye care professionals are not routinely using validated questionnaires,” O’Dell said.

“I like their comments on the patient work-up, which includes the questionnaire, tear film break-up time, staining and osmolarity,” Schachter stated. “Not every practitioner is going to have advanced diagnostic equipment; that’s just a fact. Then, lean on the other three. A recent paper [Baudouin et al.] showed that once you diagnose dry eye you can determine if it’s severe with a questionnaire and a fluorescein strip.”

Some diagnostics in the dry eye arena can be expensive, O’Dell said.

“I suggest starting with one of the diagnostic tools recommended in the TFOS DEWS II report, such as corneal and conjunctival staining and, as your practice grows and as you’re treating patients effectively, you can acquire more diagnostics along the way, such as osmolarity and noninvasive tear break-up time,” she said.

Nichols stressed that it does not take a dry eye specialty practice to look and test for dry eye.

“Certain tests involve asking a patient questions with a slit lamp to come to a diagnosis of dry eye,” she said. “There are additional specialty tests that you may incorporate, but you don’t have to. This can be done by anyone.”

The report also specified two types of dry eye: aqueous-deficient and evaporative.

A patient can have a combination of the two, but may be more skewed toward one or the other, according to Jones. In evaporative dry eye, patients are producing sufficient amounts of aqueous, but various causes are encouraging the aqueous to evaporate too quickly. Aqueous deficiency results from reduced tear volume.

“A big take-home from the report in 2007 was that there appeared to be two types of dry eye, and it was all or none, one or the other. Now we recognize that they can occur concurrently,” Nichols added.

Pain and sensation

Another new element for the report illustrates the significance of the cold thermoreceptors, which are key to the sensory information of the eye, according to Belmonte. These receptors detect wetness and maintain basal tear production and blinking rate.

“In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage,” according to the report. “Inflammation causes sensitization of polymodal and mechano-nociceptor pain nerve endings while nerve damage also causes an abnormal increase in cold thermoreceptor activity, all together evoking dryness sensations and pain.”

“The cold receptors are the sensory receptors that normally detect the level of evaporation that takes place in the eye when the eye is open and measure the concentration of salt that increases with water evaporation,” Belmonte remarked. “They possess a molecular sensor that is able to detect a very small reduction of temperature and a very small increase in osmolarity, such as those that occur when the eye is open. Cold sensory nerve fibers send signals to the brain to stimulate the production of a basal, background secretion of tears by the lacrimal glands.”

As a result of chronic dry eye, cold receptors fire abnormally due to the damage of the nerve terminals on the surface, he continued. The polymodal nociceptors are also excited because of the inflammation. This produces a chronic change in the way the cold and pain receptors fire, resulting in abnormal sensations of dryness.

Management, treatment

Currently, no research exists to guide practitioners regarding what management strategies to employ if a patient is more evaporative than aqueous deficient and vice versa.

“That evidence simply isn’t there,” Jones said. “It really made it a struggle to put the treatment algorithm together.”

He recommended that researchers should enroll study subjects with evaporative, aqueous deficient or mixed disease and in a controlled way expose them to a variety of management strategies to see which is most appropriate and most efficient.

“That’s a big chunk of the work that needs to be done moving forward,” he added.

For a large number of patients, there is no single management for dry eye, Jones continued.

Many will need to use several different strategies, even in mild cases, he said, and it is important to link the management and therapy report with the diagnostic report.

“If optometrists want to better optimize management they need to target it toward patients who either have more evaporative disease or aqueous deficient disease, and to do that they need to complete the proper diagnostic methodologies,” he said.

The TFOS DEWS II researchers created a staged management algorithm that presents steps to implement the various management and therapeutic options according to disease severity. The algorithm indicates that, first, differentiating between aqueous-deficient and evaporative dry eye is critical.

In doing so, the researchers discovered a lack of evidence “in predicting relative benefits of specific management options in managing the two dry eye disease subtypes,” according to the report.

More research needed

One strength of the report is its comprehensiveness, which allowed the experts to identify areas that need further exploration and evidence, Jones said.

“There’s an awful lot of studies that need to be done to truly underpin some of the clinical decision-making that goes on,” he said.

For example, in the case of prescribing tetracycline, Jones explained, “What is a proper dosage, how long do you need to prescribe it, and is there a particular patient profile that it works best for?”

Additionally, evidence is missing about appropriate type of omega-3 concentration.

“People will look at the report and be surprised that certain studies have not yet happened,” he added. “I’m sure that there will be an absolute flurry of great ideas for studies that need to be conducted to develop that evidence.”

Another area for future research involves mobile device use and younger patients.

“There are studies that show that computer use causes dry eye, so we need to look more at younger populations where we are seeing more dry eye than ever before,” Schachter said.

The Sex, Gender and Hormones section represents a new area for the workshop.

“A lot of what the NIH is doing is studying primarily men, but, mostly, females get dry eye,” O’Dell remarked.

“[The] sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (eg, androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (eg, microRNAs),” according to the report.

“It will be interesting to see what that does to research moving forward,” O’Dell said. “Perhaps treatments in the future may vary between male or female.”

“We don’t know much about the natural history of the disease,” Stapleton added. “The natural history of DED in treated and untreated patients remains a very important area for research.”

Potential confusion

Some practicing optometrists are concerned that the report may offer more questions than answers.

“I’m impressed with how DEWS II has taken the complexity of dry eye to another level,” Milton M. Hom, OD, FAAO, FACAAI(Sc), a PCON Editorial Board member who practices in Azusa, Calif., said in an interview. “For instance, before we can diagnose dry eye, we need to triage with a set of eight questions covering comorbidities related to dry eye. Then we have to perform an OSDI or DEQ-5 test for symptoms, followed by tear osmolarity, tear break-up or staining. I guess asking if the patient has dry eye is not enough these days.”

John Schachet, OD, president and CEO of Eyecare Consultants Vision Source in Centennial, Colo., said he has been heavily involved in managing dry eye since 1990 and is not sure if there is a true hallmark when it comes to dry eye.

“In one section I read that the hallmark of dry eye is hyperosmolarity. But in the Pain and Sensation section, it says that pain is the hallmark. Which is it?” Schachet said.

“A multifactorial disease implies that there isn’t a true hallmark. Some patients are in significant pain, some are in slight pain; I have a problem with calling these things hallmarks,” he continued.

“While most dry eye treatments are wonderful, some are better than others, and many need to be used in conjunction with each other. When you can minimize DED for a patient to live a happier, healthier life, you’ve done your job,” Schachet said.

The TFOS impact

A 15-page executive summary of the report is available online and will be published in the October print issue of The Ocular Surface.

The strength of the TFOS DEWS II report lies in clinicians and practitioners discussing and translating the document for others, Nichols said.

“Certainly, it makes sense to think that early detection and management will lead to better patient outcomes,” she said.

“TFOS brings everyone together from optometry, ophthalmology, research and industry,” O’Dell added. “You check your egos at the door ... and work together toward a common goal: improved understanding and treatments for dry eye disease. There are so many great OD leaders that have been part of the subcommittees – it’s a great representation of our industry.”

Hom added: “As Dr. Michael DePaolis says, ‘First, we are better equipped than ever to manage dry eye. Second, there is the potential for more confusion than ever.’ Despite its complexities, the new DEWS will be at the top of every ocular surface expert’s reading list.” – by Abigail Sutton

• References:
• Baudouin C, et al. Br J Ophthalmol. 2014;doi:10.1136/bjophthalmol2013-304619.
• Belmonte C, et al. Ocul Surf. 2017;15(3):404-437;doi:10.1016/j.jtos.2017.05.002.
• Bron AJ, et al. Ocul Surf. 2017;15(3):438-510;doi:10.1016/j.jtos.2017.05.011.
• Craig JP, et al. Ocul Surf. 2017;15(3):276-283;doi:10.1016/j.jtos.2017.05.008.
• Gomes JAP, et al. Ocul Surf. 2017;15(3):511-538;doi:10.1016/j.jtos.2017.05.004.
• Jones L, et al. Ocul Surf. 2017;15(3):575-628;doi:10.1016/j.jtos.2017.05.006.
• Nelson JD, et al. Ocul Surf. 2017;15(3):269-275;doi:10.1016/j.jtos.2017.05.005.
• Novack GD, et al. Ocul Surf. 2017;15(3):629-649;doi:10.1016/j.jtos.2017.05.009.
• Stapleton F, et al. Ocul Surf. 2017;15(3):334-365;doi:10.1016/j.jtos.2017.05.003.
• Sullivan DA, et al. Ocul Surf. 2017;15(3):284-333;doi:10.1016/j.jtos.2017.04.001.
• Willcox MDP, et al. Ocul Surf. 2017;15(3):366-403;doi:10.1016/j.jtos.2017.03.006.
• Wolffsohn JS, et al. Ocul Surf. 2017;15(3):539-574;doi:10.1016/j.jtos.2017.05.001.

• For more information:
• Carlos Belmonte, MD, PhD, is professor emeritus of human physiology at the medical school, University Miguel Hernandez and senior researcher of the Instituto de Neurociencias (UMH-CSIC) in Alicante, Spain. He can be reached at: carlos.belmonte@umh.es.
• Milton M. Hom, OD, FAAO, FACAAI(Sc), is in private practice in Azusa, Calif.
• Lyndon Jones, PhD, FCOptom, DipCLP, DipOrth, FAAO, FIACLE, FBCLA, is professor at the University of Waterloo and director at the Centre for Contact Lens Research. He can be reached at: lwjones@uwaterloo.ca.
• Kelly K. Nichols, OD, MPH, PhD, FAAO, is dean at the UAB School of Optometry. She can be reached at: nicholsk@uab.edu.
• Leslie O’Dell, OD, FAAO, practices at Mechanicsburg Eye Associates in Mechanicsburg, Pa. She can be reached at: leslieod@hotmail.com.
• John L. Schachet OD, has owned a private practice in Centennial, Colo. since 1974. He can be reached at: jschachet@aol.com.
• Scott E. Schachter, OD, practices at Advanced Eyecare and The Eyewear Gallery Optometry in Pismo Beach, Calif. He can be reached at: applescott@me.com.
• Fiona Stapleton, MCOptom, PhD, DipCLP, FAAO, FBCLA, is a professor and head of the School of Optometry and Vision Science at the University of New South Wales in Sydney, Australia. She can be reached at: f.stapleton@unsw.edu.au.

Disclosures: Belmonte has a patent, is a consultant for and/or reports financial interest in Avizorex, CooperVision and Matrix Biology Institute. Hom is a consultant for AGN, Bausch + Lomb, Shire and Sun Pharmaceutical Industries. Jones receives financial support from Advanced Vision Research, Alcon, Allergan, Contamac, CooperVision, Essilor, Inflamax, Johnson & Johnson Vision Care, Ocular Dynamics, Oculus, Safilens, TearLab and TearScience and is a consultant or researcher for Alcon, CooperVision and Johnson & Johnson Vision Care. Nichols is a researcher for or has financial interest in Alcon, Allergan, Bausch + Lomb/Valeant, BruderHealthcare (spouse), ElevenBiotherapeutics, Insite Pharma, Johnson & Johnson Vision Care (spouse), Kala, Oculus, Santen, ScienceBased Health, Shire, Tearfilm Innovations, TearScience and Vistakon. O’Dell reports she is a speaker for Allergan and Shire and a consultant for Allergan, Paragon BioTech and Shire. Schachet reports he is a consultant for Oculus, TearLab, and TearScience and speaks and works for Vision Source. Schachter serves on the advisory board for Allergan, BlephEx, RySurg, ScienceBased Health, Sun Pharma and TearScience and is a speaker for Allergan, Bausch + Lomb and BioTissue. Stapleton reports financial interest in Alcon, Allergan, CooperVision, Johnson & Johnson Vision Care and Stiltec and she is a consultant for Nidek.