Article

A complicated disease gets more so

DEWS II committee has a new definition for dry eye.

Homeostasis. Ocular wellness. Corneal nerve hypersensitivity. Neurosensory abnormalities.

All these terms have helped shape the new definition of dry eye.

This updated description, which was researched, reviewed and written by the 150-plus members of the international DEWS II committee, considers the condition’s multiple etiologies. The committee, which took nearly three years to finish its work, views dry eye as a disease on a continuum, and recognizes that hypersensitivity of the corneal nerves may explain why patients come forth with complaints of dry eye in the absence of clinical signs of dry eye. It also recognizes the complexities of the ocular surface, learned through years of research.

The definition is not the committee’s only new news about dry eye, but, at this point, it is the only publicly announced information. Presented in part at the ARVO meeting in May, the report is slated to appear in its entirety in print this month. It is officially known as the Tear Film & Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II).

A DECADE’S WORTH OF KNOWLEDGE

“This [DEWS II report] is a very comprehensive review of … the last 10 years,” says J. Daniel Nelson, MD, FACS, DEWS II chair. He expects the updated definition will create consistency in clinical trial designs.

“This definition will provide much more clarity for future research and create a standard for industry,” he says.

KEY OBJECTIVE

Redefining dry eye was a critical objective of the committee.

The new dry eye definition is as follows:

“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.”

And the first DEWS I definition:

“Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.”1

Dr. Nelson, who is also senior medical director, Health Partners Medical Group and professor of ophthalmology at the University of Minnesota in St. Paul, MN, says published literature about dry eye has doubled since the first DEWS report was released in 2007.

“In the past, we thought of hyperosmolarity and inflammation as markers of the disease, but we know now that they are part of [its] etiology,” he says. Hence, the new definition underscores the multiple factors involved in dry eye.

“Ophthalmologists should think about what the patient has and should not think that everyone complaining of dry eye symptoms needs to have their eyes ‘watered.’”

ON BALANCE AND WELLNESS

The definition also introduces the term homeostasis, which thought leaders like Preeya K. Gupta, MD, say reflects the actual condition as one that is on a continuum. The idea of tear film homeostasis is a major difference between the old and new definition.

“I think it is a great concept because it really encourages the clinician to look at the different contributors of dry eye and look at them on balance,” says Dr. Gupta, a member of the DEWS II diagnostic and public awareness subcommittees.

Before, clinicians were rigid in their decision that dry eye fell into one of two categories: aqueous deficient or evaporative dry eye.

But, says Dr. Gupta, an assistant professor of ophthalmology, cornea and refractive surgery at Duke Eye Center in Durham, NC, “the reality of it is that the disease is often a mix of both, with some components of evaporative and aqueous deficient.”

The term homeostasis also emphasizes ocular surface wellness, creates an objective of an optimal state that clinicians are trying to achieve in their patients and does away with the “false dichotomy” of dry eye as being either evaporative or aqueous deficient, according to Richard Adler, MD, FACS, director of ophthalmology at Belcara Health and assistant professor of ophthalmology at Wilmer Eye Institute in Baltimore, Md.

“There is a physiologic equilibrium that we should be aiming towards,” says Dr. Adler. “Once we start to reframe the disease in terms of homeostasis and ocular wellness, we can think about prevention and what we can do proactively instead of reactively. Emphasizing physiological wellness [of the ocular surface] should be a goal.”

THE VALUE OF CORNEAL HEALTH

Ocular surface wellness is especially key for optimizing surgical outcomes. If a patient has pre-existing dry eye, for example, that problem can deter from optimal outcomes in cataract surgery, underlining the need to manage dry eye before surgery, stresses Dr. Gupta.

“We realize that our presurgical patients are at higher risk [for developing dry eye] than average patients,” he says. “We should screen them more aggressively because there are risks to them being dry, such as a poor visual outcome or increased dry eye symptoms after surgery.”

P THEN Q SITUATION

The new definition incorporates the multiple causes that can lead to dry eye. Logically, what should follow is the development of multiple treatment choices, suggests Dr. Gupta.

“This definition may influence how companies, especially in the research and development phase, develop therapies for dry eye,” says Dr. Gupta. “The definition gives us more insight into the different types of dry eye patients that exist today.”

FORWARD THINKERS

A new etiology, at least for dry eye, is neurosensory abnormalities, which Dr. Gupta describes as a forward-thinking move.

“There is a subset of patients who have chronic pain and discomfort that do not necessarily respond to traditional therapies. The definition gives a nod to the neuropsychological component of the disease. We know that people who suffer from dry eye may also have abnormal pain sensitization, depression and/or anxiety. It is important to be clinically aware of that.”

These patients often perplex clinicians by presenting with complaints of dry eye and likely have eye pain that is mediated by abnormalities or nerve hypersensitivity, explains Christopher E. Starr, MD, associate professor of ophthalmology, director of the cornea fellowship, director of refractive surgery and director of ophthalmic education at Weill Cornell Medicine in New York, NY.

These patients do not show the classic objective clinical signs of dry eye, such as elevated inflammation, typically measured via matrix metalloproteinase-9 analysis or diffuse staining of the cornea using sodium fluorescein, osmolarity readings greater than 308 Osm/L or variability in osmolarity between eyes, notes Dr. Starr.

“These are patients whose osmolarity is normal, and they do not have inflammation,” says Dr. Starr, a member of the DEWS II public awareness and education subcommittee. “We have learned a lot more since DEWS I about the complexity of the ocular surface. Other pain processes may cause similar symptoms of traditional dry eye but may need to be treated in a different way.”

Dr. Starr says that, diagnostically, these patients who complain of dry eye symptoms and have suspected neurosensory abnormalities may be detected through abnormal innervation of the cornea as seen with abnormal-imaging results on confocal microscopy.

DIVIDE BUT CONQUER

Ophthalmologists struggle with the divide that can exist for some patients in terms of signs and symptoms of dry eye disease, and this broadened definition of dry eye disease addresses that disconnect to a degree, by incorporating novel elements like neurosensory abnormalities.

“However, we may still struggle with this disconnect,” says Dr. Adler. “As written, the definition still implies that ocular symptoms ‘accompany’ the signs, and that’s just not always the case.”

Along with hypersensitivity, some patients can possess hyposensitivity and may have signs of dry eye but do not complain of any symptoms of dry eye, adds Dr. Adler.

WHAT TO EXPECT

The DEWS II report, which will be translated into several languages, will also touch on iatrogenic triggers for dry eye including surgeries, both medical, such as cataract, and cosmetic, such as blepharoplasty.

The iatrogenic report notes that dry eye can develop as a side effect of some medications and that exposure to cosmetic products, many of which contain toxic compounds, can elicit symptoms of dry eye.

The entire DEWS II report, slated for publication in the July issue of The Ocular Surface, will also be available online at www.TearFilm.org . OM

REFERENCE

  1. 2007 report of the International Dry Eye Workshop. Ocul Surf. 2007;5(2):65-206.

OTHER REFERENCES

  1. Rosenthal P. Dry eye symptoms after keratorefractive surgery. Ophthalmology Management. June 2007. http://www.ophthalmologymanagement.com/issues/2017/june-2017/visionaries-and-educators .
  2. Luthe R. New model simulates human conjunctiva. Ophthalmology Management. June 2007. http://www.ophthalmologymanagement.com/issues/2017/may/new-model-simulates-human-conjunctiva .
  3. DED, beyond itch and explanation? A round table with Perry Rosenthal, MD. Ophthalmology Management. May 2017. p. 36.