Clinicians better understand intricacies of dry eye

May 15, 2005

Boston-Gaining a greater understanding of dry eye will allow practitioners to manage this condition effectively, said Kathryn A. Colby, MD, PhD, director, Joint Clinical Research Center, Massachusetts Eye and Ear Infirmary, Boston.

She delivered a three-part message for physicians who treat this prevalent eye condition.

"The tear film is a hydrated gel with complex biology; the integrated lacrimal functional unit must be intact for a healthy ocular surface; and dry eye is an inflammatory disease. Incorporating these ideas will help you provide better care for your patients with dry eye," said Dr. Colby, who offered an update on the latest developments in dry eye therapy and a look into the future during the American Academy of Ophthalmology annual meeting in New Orleans.

Functional lacrimal unit Investigators also have learned more about the integrated functional lacrimal unit, which is composed of the sensory nerves of the ocular surface, the lacrimal glands, the meibomian glands, the conjunctival goblet cells, and the nerves that connect these structures.

"All these structures form an integrated functional unit that requires input from the central nervous system to perform its duties of providing good vision, guarding against infection, and maintaining ocular comfort," Dr. Colby said. "Perturbations anywhere along this pathway disturb the homeostasis of the ocular surface and cause ocular discomfort, redness, and contact lens intolerance that are characteristic of dry eye."

She also noted that multiple lines of evidence support the role of inflammation in the pathogenesis of dry eye.

"Although not all of the details are understood as of yet, we do know that changes in the tear film composition that accompany dry eye act to promote inflammation of the ocular surface. These include decreased secretion of natural anti-inflammatory factors, increased production of proinflammatory cytokines and proteolytic enzymes, and activation of normally inactive cytokines that are present as part of the ocular surface defense mechanisms," Dr. Colby explained.

Subsequent increases in tear film osmolarity also perpetuate ocular surface inflammation by increasing inflammatory cytokines and matrix metalloproteinases. Finally, loss of androgenic support facilities the creation and maintenance of an inflammatory milieu and may be at the root of the clinical observation that dry eye disease is more common in women.

Inflammatory cascade Ultimately, the inflammatory cascade resulting from perturbations in the integrated functional lacrimal unit causes the familiar patient symptoms, Dr. Colby said. She also observed that a better understanding of the complex nature of the tear film has led to the creation of a new generation of tear supplements that not only provide lubrication but also act to stabilize the tear film.

"Now that we understand that inflammation plays a significant role in the pathogenesis of dry eye, we can exploit several classes of anti-inflammatory medicines to treat our patients with dry eye," Dr. Colby said.

Topical steroids, which have multiple modes of action, are known to be effective in treating the signs and symptoms of dry eye but are a double-edged sword with potential side effects such as glaucoma and cataract. Newer-generation "soft" steroids reduce the incidence of these side effects.

"Oral tetracycline derivatives have anti-inflammatory properties," Dr. Colby said. "They reduce cytokine production and inhibit matrix metalloproteinases. They modulate bacterial lipase activity and change the composition of meibomian secretions, thus stabilizing the tear film.

"While generally well tolerated, they can cause photosensitivity, gastrointestinal distress, yeast infections, and can interfere with the efficacy of certain oral contraceptives," she continued. "However, they remain an important tool in our armamentarium, especially for patients with meibomian gland disease."