Innovation Spotlight - Dry Eye

Dry eye: investigators look at syndrome with new model

By Chet Scerra
Reviewed by William D. Mathers, MD

William D. Mathers, MD

Las Vegas-Researchers need to develop a new model for dry eye syndrome that incorporates multiple disease processes, according to William D. Mathers, MD.
"None of the explanations that we have for dry eye symptoms is completely correct, and we need a new model to put them all together in some kind of global way," said Dr. Mathers, a cornea/external disease specialist who is professor of ophthalmology at the Casey Eye Institute affiliated with Oregon Health Sciences University, Portland.
Because the symptoms are not specific, it is hard to determine the prevalence of dry eye syndrome. Clinicians do not have one particular measure to evaluate dryness. The range of physiology is quite broad, he continued. Dr. Mathers was the Conrad Berens Lecturer at the annual meeting of the Contact Lens Association of Ophthalmologists (CLAO).
According to estimates, 28% of menopausal women have dry eye symptoms, but only 14% of the older population does. About 5% of patients with contact lenses have to stop wearing them each year because of dry eyes. There also is a close relationship between blepharitis and dry eye.

A new model

The lacrimal gland and cornea are both responsible for creating dry eye symptoms. Lacrimal gland disease can alter the ocular surface, Dr. Mathers said.
"We also are saying that the ocular surface disease alters the lacrimal gland. Understanding this is the key to making sense of the model," he said.
Normal tear homeostasis is controlled, at least partly, by tear osmolarity. Increased tear osmolarity causes increased stimulation from the ocular surface and increased tear flow, which in turn causes decreased osmolarity. This cyclical relationship creates feedback to the lacrimal gland.
"All tear flow is basically stimulus driven," Dr. Mathers said. "Sleep, for example, causes a profound decrease in tear flow, as do both general and topical anesthesia. Without stimulation, the tear flow shuts down almost to zero. There really is not an entity known as non-reflex tearing."
There are other factors that can cause decreased tear flow. Systemic and local immune disease damaging the lacrimal gland will decrease the flow.
"Decreased tear flow has significant consequences," he said. "It results in decreased washout of the ocular surface, causing an increase in the level of cytokines and a decrease in growth factor [from the lacrimal gland] in the tear film.
"Increased cytokine levels can damage the corneal nerves. This decreased corneal sensation can be seen in patients with Sjögren's syndrome, as well patients with herpes simplex, herpes zoster, diabetes, or after refractive surgery. In these cases, an increase in cytokines inhibits neural transmission in the parasympathetic nerves," he said.
"Corneal damage can alter the lacrimal gland," Dr. Mathers added. "We do not know exactly how this works, but there are data to support this process. When you wound the corneal epithelium, you see changes in growth factor in the lacrimal gland. Altered lacrimal gland innervation may cause a release of substance P, which can stimulate lymphocytic infiltration of the gland. Also, decreased sensory input may cause atrophy of the gland."

Contact lens factor

For example, contact lenses may lead to decreased washout. This can cause increased cytokine build-up, which can lead to corneal nerve damage. There is a possibility that contact lens use could lead to lacrimal gland damage and dry eye.
"Contact lenses must function perfectly if we want to avoid creating a system where the cornea and lacrimal gland are perturbed," he said.
"This relationship may explain why so many people stop wearing contacts. This is a major opportunity to manufacture contact lenses that don't disrupt this physiology," Dr. Mathers continued. "Also, corneal sensation is definitely altered for months with LASIK and other refractive procedures. Patients with dry eye need special care here."
There are several causes for dry eye syndrome, such as evaporation stress, loss of hormone support to the lacrimal gland, simple aging effects, overstimulation of the gland, virus infection of the lacrimal gland, blepharitis, and loss of lacrimal gland growth factor to the ocular surface.
Evaporation accounts for a small amount of liquid. In the normal eye, one-third of resting tear flow evaporates. But in dry eye, approximately three-quarters of the tear film is evaporating.
"The total steady-state tear flow (the sum of evaporation and flow) is actually equal in normal subjects and patients with dry eye. This is a relatively small volume," Dr. Mathers said.

Hormonal loss

The lacrimal gland has androgen receptors but not estrogen receptors.
"Prolactin may play a role in antagonizing the androgen action," Dr. Mathers said. "Estrogen replacement does not alter the incidence of dry eye in women."
Overstimulation of the lacrimal gland may create abnormal cellular trafficking. This might stimulate immune disease, but there are no convincing data, he said.
As far as the effects of age, most older people do not have dry eye syndrome. However, most tear variables do change with age. There have been few studies to determine how the lacrimal gland ages.
"Osmolarity increases over the years, and tear volume decreases. As tear flow decreases, the evaporation rate goes up and the Schirmer score goes down. An average tear flow of 24 mm in a 20-year-old might drop to 8 mm in an 80-year-old," he said.
"Age certainly does seem to have an effect in dry eyes, but it still doesn't explain the condition," he said.

Blepharitis

Blepharitis and dry eye have very similar symptoms and can be very difficult to distinguish.
The typical patient with blepharitis has increased tear evaporation with obstructive meibomian gland dysfunction. Seborrheic meibomian gland dysfunction is associated with dry eye. Loss of the tear film leaves the lid margin more inflamed.
"By treating the blepharitis, you are interrupting the blepharitis feedback loop to the lacrimal gland," Dr. Mathers said. "You may help both the lacrimal gland and the meibomian gland.
"Punctal occlusion may alter the feedback loop in a way you may not want," he continued. "Our punctal occlusion data show no change in osmolarity, even though the tear volume increases.
"Occlusion may be giving us results that aren't so good," he said.
Research based on a comprehensive theory is important.
"In the past, everyone has been working in their own little corner," Dr. Mathers said. "We need a mechanism that can pull it all together.
"Clinical data and cell biology must complement each other. The process may be complex, but it is capable of being studied," Dr. Mathers concluded. "Understanding this process will benefit patients tremendously."

Ophthalmology Times / APRIL 1, 2000