Washington, DC—Dry eye disease affects millions of people worldwide and with that has come a recent greater awareness among patients that
it is indeed a problem. As the recognition of the magnitude of dry eye is changing, so too has knowledge of its pathogenesis,
the technology facilitating diagnosis, and the drugs that are becoming available to treat it. General ophthalmologists will
be increasingly challenged to learn more about the disease and the best ways to treat individual patients, according to Michael
Lemp, MD.
"Patients have recognized over the years that they have had a problem but have not been able to articulate it well to physicians.
In terms of the extent of the problem in society in general, we have become much more aware of dry eye in recent years. Practicing
physicians can document dry eye as a frequent complaint among patients," said Dr. Lemp, clinical professor of ophthalmology,
Georgetown University and George Washington University, Washington, DC. "In addition, the American Academy of Ophthalmology
recently reported that 30% of patients complain of ocular irritation to ophthalmologists. This represents a substantial percentage
of patients in office practices."
The unmet need
Only recently, however, have studies been published that cast light on the prevalence of actual dry eye disease. Specifically,
Debra Schaumberg, ScD, OD, MPH, and colleagues evaluated more than 40,000 women who participated in the Women's Health Study
and extrapolated that there are in excess of 9 million individuals in the United States with moderate to severe dry eye. However,
the scope of the problem becomes even more evident when one considers that for every patient with moderate or severe symptoms
of dry eye, there are likely three to four times as many with mild or intermittent symptoms, bringing the numbers to 30 to
60 million affected people. The pharmaceutical companies have already recognized the market potential and have responded with
numerous formulations that attempt to relieve symptoms, Dr. Lemp pointed out.
With increasing recognition of dry eye, Dr. Lemp also explained that there will be a significant impact on how ophthalmologists
and optometrists practice, because until now only about 5% of those with symptoms have had dry eye diagnosed.
"It is going to be an increasing challenge for doctors to diagnose dry eye," he said. "Most standard tests used in the office
are not positive except for patients with moderate to severe symptoms. Patients with mild to moderate disease do not test
as abnormal, which results in the physicians making an educated guess as to the cause of the symptoms in the absence of findings."
Hand in hand with this is the attitude among ophthalmologists that dry eye is not a disease, according to Dr. Lemp, but rather
a concomitant of aging and an inconvenience for patients. Consequently, general ophthalmologists have not addressed dry eye
as a condition that can worsen because of the specific pathogenetic mechanisms that are operative and can result in tissue
destruction.
"Many doctors have felt constrained because they believe there has been a lack of effective treatments and only artificial
tears were available to ease symptoms," he said.
Patient complaints
The results of Schirmer testing and staining of the ocular surface often do not reflect the patient complaints of dry eye
symptoms.
"There is increasing evidence that no matter what the initiating systemic causes or associations with the beginnings of dry
eye, when tear film/ocular surface abnormalities begin and there is discomfort, several global features of dry eye occur,
namely, tear film instability, which results in more rapid breakdown between blinks, and elevated tear film osmolarity. These
factors probably occur before there is a consistent decrease in tear production and before breakdown of the ocular surface,"
Dr. Lemp explained.
Many patients do not have progress beyond that stage to consistently decreased tearing and breakdown of the ocular surface;
nevertheless they have symptoms.
Of great interest to Dr. Lemp are the visual changes that occur in patients with dry eye. On testing of typical patients,
the visual acuity is 20/20. With rapid breakdown of the tear film between blinks, the image on the retina becomes distorted;
patients respond by blinking more often to re-form the tear film. With chronic increased blinking comes ocular fatigue, one
of the most common symptoms of dry eye, he explained.
A Japanese study (Ishida et al., Am J Ophthalmol 2005; 139:253-258) reported on tear film breakdown between blinks using a functional visual acuity measurement. When patients
held their eyes open for 30 seconds, the authors presented targets at 10, 20, and 30 seconds and the visual function was compared.
The investigators reported that "the mean functional visual acuity scores were significantly lower in patients with dry eye
than the controls at each time point (p < 0.05)." At 10 seconds, the functional visual acuity decreased in the patients with dry eye from the baseline value of 0
to –0.2, at 20 seconds to –0.4, and at 30 seconds to –0.5.
"Depending on the severity of the dry eye, individuals can have a distorted image 30% to 40% of the time between blinks. This
study has allowed the first documentation of the decreased visual acuity," Dr. Lemp emphasized.
Regarding measurement of tear film osmolarity, there has not been a practical way to measure osmolarity accurately in the
office. A new test to measure osmolarity is presently under development by OcuSense that should simplify the tasks of diagnosis
and management of dry eye for physicians. The hope is that the device will be available within a year.
"This test will also be useful in the future when there are additional dry eye treatments on the market," he said. "For example,
topical cyclosporine (Restasis, Allergan) is prescribed twice daily, but it is unknown how long that dose should continue
or when patients might be able to instill the drug once daily. This new test may give physicians a better picture of what
is happening on the surface of the eye and help them choose a regimen."
Dry eye algorithm
So what is the best way to approach treatment?
A good patient algorithm, according to Dr. Lemp, is one forwarded by Stephen Pflugfelder, MD. When a patient with ocular irritation
presents, the tear film break-up time is tested. If it is not unstable, the irritation is the result of another problem. If
the tear film is unstable, further investigation is required, starting with tests of tear production. If tear production is
normal, there is no deficiency of lacrimal gland production but likely excessive evaporation.
"Recent studies have shown that most patients have a mixed type of dry eye, rather than solely decreased tear production or
increased tear loss through evaporation. This has resulted in a shift in thinking toward classifying patients as having mild,
moderate, or severe dry eye for the purposes of treatment decisions, because it is likely that they have a mixed form of the
disease.
"The focus now is an algorithm that classifies patients by disease severity," Dr. Lemp explained.
An important aspect of diagnosis is the consideration that dry eye results from systemic disease that can go undiagnosed.
These diseases include thyroid disease, Sjgren's syndrome, diabetes, trachoma, sarcoidosis, vitamin A deficiency, and atopy.
In many cases, the dry eye symptoms can be the first sign of the presence of a systemic disease, so careful questioning of
patients to uncover all their symptoms may reveal the primary disease process.
"Although the percentage of patients with a recognizable systemic disease is relatively small, this is important. These are
the patients who will be the sickest and who cannot afford to have the systemic condition overlooked," Dr. Lemp emphasized.
The treatment landscape began to change slowly with the introduction of topical cyclosporine, the first truly therapeutic
drug that addresses the underlying inflammation in dry eye.
Prior to its introduction, various tear film formulations were available that relieved dry eye symptoms.
"When these drugs become available, ophthalmologists will be challenged because the drugs will have different mechanisms and
different treatment strategies. Physicians will have to learn more about dry eye in order to determine which treatment(s)
is better for individual patients," Dr. Lemp said.
A number of new artificial tear formulations have also entered the market. Some of the new over-the-counter medications do
not simply replace the tear volume.
"They actually have components that work on the pathogenetic mechanisms in dry eye. Systane Lubricant Eye Drops (Alcon Laboratories)
has had a lot of success since it was introduced; the product has a unique polymer system that is pH dependent and forms a
gel on the ocular surface and prolongs the break-up time of the tear film. Soothe Emollient Eye Drops (Alimera Sciences) has
a lipid component that replaces defective lipids in dry eye and retards evaporative tear loss," he explained.
In addition, Dr. Lemp noted, there are an estimated 15 drugs in the testing pipeline, which in the next few years should result
in a variety of available products for dry eye.
A future treatment option that is receiving attention is hormone treatment because androgen deficiency is implicated in dry
eye. Allergan is presently testing a topical androgen product that may reverse secretion problems in the lacrimal glands and
meibomian glands. In addition, a number of mucin stimulators are in clinical trials.
"In about 6 or 7 years, when more of these products are available, the best treatment strategy may be the use of two or three
different products, for example, a drug for the short term that acts quickly, stabilizes the tear film, and decreases the
osmolarity in combination with a product that is used less frequently, has a longer-lasting effect, and suppresses inflammation,"
Dr. Lemp stated.
What's in a name?
Clearly, a great deal. Some authors have advocated a name change for dry eye to dysfunctional tear syndrome because the latter
is more descriptive of the mechanism of the disease. However, the opposition has been substantial.
"There are patients with certain subsets of dry eye who have changes in the quality of their tear film and the eye is not
as dry as the name would indicate," Dr. Lemp said. This idea of changing the name was discussed, he explained, at a meeting
of the Dry Eye Workshop in fall 2004. However, the name change was rejected by a majority of the worldwide attendees of the
meeting because the name dry eye is well recognized by most medical specialists and not just ophthalmologists. In addition,
ophthalmologists from non-English-speaking countries pointed out that the English words dry eye have been incorporated into the medical and lay literature.
"The issue regarding the name now is less about the most descriptive name but more about what is the most useful name. This
might, however, change with time," Dr. Lemp concluded.
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