Article Date: 7/1/2000

New Concepts in Dry Eye Research

discovering dry eye

New Concepts in Dry Eye Research

BY BARBARA CAFFERY, OD, MS
July 2000

There is nothing like attending ARVO, which in my mind is the best eye research meeting in the world, to realize the shifting paradigms in ocular disease. From myopia to glaucoma, scientists are finding  new ways to look at ocular diseases.

The New Understandings in the Pathophysiology and Treatment of Dry Eye Disease seminar presented new concepts that can help clinicians understand this ocular surface condition.

Stimulating Goblet Cells

Darlene Dartt, PhD, presented a paper on the neurological control of conjunctival goblet cells in rats. Goblet cells manufacture mucin sacs that travel to the cell membrane and explode into the tear film, releasing all the granules in the cell. Dr. Dartt explored the role of nerves in stimulating goblet cells. Her theory is that the cornea, stimulated by some form of dry eye, sends sensory information to the central nervous system which then sends efferent messages to the ocular surface.

Dr. Dartt demonstrated the proximity of muscarinic and vasoactive intestinal peptide (VIP), parasympathetic nerve endings around the goblet cells of the rat. In normal states, low stimulation of the cornea and conjunctiva causes the central nervous system to send mild parasympathetic stimuli for regular goblet cell secretions. A wounded cornea has little sensitivity. The system slows down and we end up with drier eyes as in Sjögren's syndrome. In GPC where the cornea is continually irritated, much more mucous is secreted.

Inflammation and Dry Eye

Michael Stern, PhD, of Allergan Pharmaceuticals described dry eye disease as a local inflammatory process. Reduced levels of androgens, steroid hormones that protect the ocular surface from inflammation, occur with age. When the level is reduced as in menopause, ocular cells make more cytokines that attract T cells into conjunctiva, producing symptoms of dry eye disease.

Dysfunction occurs in the salivary and lacrimal glands early in dry eye disease. A programmed cell death or apoptosis occurs that allows an influx of lymphocytes into these glands, causing their dysfunction. This may explain why cells such as the acinar cells of the lacrimal gland do not function even when not destroyed by the lymphocytic infiltration.

Stephen Pfluegfelder, MD, discussed inflammatory changes on the ocular surfaces of dry eye patients. Compounds in normal tear film, including lactoferrin, TIMP IL-1 and TGBF, reduce inflammation. Lactoferrin was significantly reduced in the tear film of Sjögren's subjects.

Subjects with reduced tear clearance had altered protein profiles in their tear compositions.

In rosacea, stress and infection can decrease tear clearance and increase interleukin 1. This produces fever and increased inflammation mediated by cytokines and IL-6 and 8, causing chemotaxis of T cells.

Interleukin-1 in dry eye, Sjögren's syndrome and rosacea is high compared to normals. Unlike normals, in dry eye tear films it is in its mature form. This increases the inflammatory process.

Relief with Cyclosporin

Another lecture discussed the use of cyclosporin as a topical anti-inflammatory in dry eye disease. Using impression cytology, various inflammatory markers such as HLA, CD40 and FAS were found in the cells of the ocular surface. Treatment with cyclosporin reduced inflammatory markers and symptoms.

Although many of these concepts are preliminary, keeping informed of the new ideas that scientists are working on will change our concepts of diseases and improve treatment. 

Dr. Caffery has practiced optometry in Toronto, Canada, in a group setting dedicated to contact lens and tear film research since 1977.


Contact Lens Spectrum, Issue: July 2000