A multitude of causes, symptoms complicates dry eye diagnosis

Issue: May 1998

BySusan E. Marren, OD FAAO

TORONTO - A few conjunctival or corneal cells suffer an insult, and neurons fire. The brain receives the signal, and the message reaches consciousness that the eyes are "dry." But is the original sensation a stinging, burning, sandy or gritty feeling? Do the eyes ache, or feel a piercing pain? Are they sticky, gunky or just dry? Contact lens patients may say, "My eyes feel dry." What is happening?

Barbara Caffery, OD, MS, and a group of researchers from the American Academy of Optometry are asking themselves just these questions. "We are in a vicious cycle," she said. "We define dry eye disease by what we see, and what we see defines the disease."

Three categories of conditions

The group has chosen to attack the problem from the standpoint of symptoms, hoping to find that specific symptoms lead to diagnosis. So far, they have divided dry eye conditions into three categories:

A condition resulting from inflammation caused by an autoimmune condition. This may include "Sjögren's," said Dr. Caffery, "where you have systemic changes in the immune system that primarily attack the lacrimal gland and the conjunctiva and secondarily attack what's in the tears."
A condition related to the tear film. "If you hold your eyes open, you feel your eyes burning and stinging," she said. "That is probably the result of the tear film evaporating, and the ocular surface signals the brain, where it's interpreted as burning, stinging or dryness."
A condition associated with contact lens wear. "These patients will say their eyes feel sticky and dry but they rarely say their eyes burn," Dr. Caffery said. "Maybe this is because of a build-up on the contact lens itself. The signal says the eye is 'dry' while the eye is not necessarily dry."

Dr. Caffery believes the Sjögren's patient specifically complains of pain in the morning from exposure to inflammatory components in the tear film during the night. Then, as the day goes on and the tear film is affected by evaporation, you get an increase in symptoms again toward the end of the day. After working in a Sjögren's clinic and then seeing a lot of dry eye in her private practice, Dr. Caffery has begun speaking to optometrists about the Sjögren's patients they are probably missing.

Frank J. Holly, PhD, of the Dry Eye Institute in Lubbock, Texas, reports that the majority of the so-called "dry eyes" do not "dry out." He says the tear film ruptures or becomes discontinuous due to the transformation of ocular surface areas that are no longer wetted by the tear film. "The exposed epithelial surface of these dry spots will suffer cellular damage even if they are kept under 100% relative humidity, that is, no loss of water from the tissue (drying) occurs," he said. Dr. Holly suggests that such an impaired cellular ocular surface leads to unstable tear film, and a pathologically short tear break-up time eventually results in ocular surface damage - a vicious circle.

Dr. Holly has also demonstrated that normal meibomian lipids in combination with tear proteins stabilize the tear film as it lowers the film energy. However, when the polar fraction of meibomian lipids pathologically increases, they adversely affect tear film stability, causing or exacerbating dry eye symptoms.

While his theories on etiology are very different, Jeffrey P. Gilbard, MD, describes the tear film in dry eye syndrome associated with meibomian gland dysfunction (MGD) as "watery and splashy because the meibomian oils, besides retarding evaporation, reduce surface tension of the tear film and help it to stay tight to the eye," he said.

Dr. Gilbard believes symptoms from meibomianitis are worse upon awakening because the cornea and conjunctiva have been in contact with the eyelids through the night. Symptoms from dryness from MGD get worse as the day progresses because, with the eyes open, evaporation "pulls ahead of" tear production and tear osmolarity increases, he said.

Dr. Gilbard theorizes that "the cornea is resistant to damage from increasing osmolarity because the corneal cells are held together by tight junctions. Conjunctival cells aren't, so the osmotic gradient will rip the cells apart."

Hormonal regulation

William D. Mathers, MD, believes several approaches to determining the cause of dry eye will be important: the immunology and the hormonal drive that supports lacrimal function. "Animal work would indicate that, at least in dogs, an immunological basis for dry eye can be treated with immunologic suppression," he said. "Particularly in Sjögren's syndrome and possibly in other conditions, the lacrimal gland is affected by an autoimmune process. Some work would indicate that overstimulation of the gland might lead to an autoimmune process.

"I believe we will understand more about the origin of the immunological attack on the lacrimal gland in the next few years," he continued. "As hormonal support falls with increasing age, lacrimal gland function declines. Some individuals may overstimulate their lacrimal glands to compensate and then create an autoimmune process that further degrades their system. In this case, blepharitis, MGD and evaporative conditions may play a role. This is not clear yet."

The role of estrogen - especially orally - is not yet defined. Dr. Mathers has found oral estrogen to be of benefit to postmenopausal patients with dry eye.

According to Michael A. Lemp, MD, he role of estrogen is controversial. "Estrogens may have a deleterious effect on immunological disease as evidenced by predominance of diseases like lupus and Sjögren's syndrome in more women than men," he said. "Estrogen seems to be an up-regulator of the immune system while androgens seem to be down-regulators."

Dr. Mathers believes it is not that simple. "I find a negative correlation between prolactin levels and tear flow," he said. "So the action of hormone on the lacrimal gland is going to be a complicated interaction."

Dr. Gilbard does not believe that corneal/conjunctival surface inflammation has anything to do with etiology. "We know how the ocular surface changes from dry eye based on human studies - both light microscopy and electron microscopy," he said. "We can reproduce those changes in animal models. So the ocular surface changes reflect the final common pathway: loss of water from the tear film, increased osmolarity, osmotic dehydration of the surface associated with damage to the cells."

New tools

Tear osmolality is a quality you can now test, thanks to Advanced Instruments Model 3000 Nanoliter Osmometer. Product Manager Ken Micciche said although the correct term is osmolality, many use osmolarity and osmolality interchangeably. The unit should be available for practitioners very soon. Right now, it is in use in five labs where it is being tested for reliability and repeatability, and testing methods are being streamlined.

"Right now, there is a learning curve in how practitioners load the sample," Mr. Micciche said. "We're proficient at it, but we want these labs to validate our concerns and provide ideas on how to optimize the sample collection/loading process."

The unit comprises a computer, microscope and camera and measures the osmolality of a 200-mL tear sample. It will be of great benefit in diagnosing and managing the dry eye patient.

Another new tool that is already on the market is EagleVision's TearScope Plus Total Tear Film Kit. The practitioner may use this device with a slit lamp to view the tear film and assess its thickness, quality and oil patterns noninvasively. The instrument, which includes a timer for measuring noninvasive tear break-up time, is an asset to diagnosis and management of dry eye as well as contact lens patients.

Lissamine green stain is rapidly replacing the use of rose bengal stain. Cristina M. Schnider, OD, MSc, who wrote the chapter about dyes for the Bartlett and Jaanus textbook, Clinical Ocular Pharmacology (Butterworth-Heinemann, Boston), said, "Rose bengal was thought to be a vital stain, which means that it doesn't harm living tissues, but numerous studies have been done to show that it actually kills living tissues and what you see are dead cells that were killed by rose bengal. It is also very photosensitive, so its activity changes according to light."

Zone Quick is a phenol red thread test developed by Hamano in Japan and distributed by Menicon USA and other select distributors.

The Zone Quick threads are yellow and turn red with wetting to make them easy to measure. Zone Quick takes 15 seconds. Less than 10 mm of wetting is abnormal, between 10 and 19 is uncertain and should be retested, and greater than 20 is normal, based on normative data from the United States.

Diagnostic routine

Albert Morier, OD, of Albany Medical College, believes dry eye is much more prevalent than we would think. "The biggest surprise is that a lot of people have this but think their symptoms are normal," he said. "I often think I never would have found a particular dry eye patient if I had not asked the right questions."

He uses a questionnaire that asks about symptoms such as dryness, scratchiness, burning, stinging and more light sensitivity at some times than others. Other questions include: Do your eyes feel differently at work than during the weekend? Do you have more trouble at the computer than with other reading?

Dr. Morier feels that both the phenol red thread and the Schirmer's test have a high incidence of false negatives, so he performs both and believes whichever results indicate the dryest eye if the patient has symptoms. Like many others, he finds that rose bengal is not necessary and too painful when the eye is dry.

Clues from the face, slit lamp

All clinicians and researchers are putting more emphasis on gross facial and slit-lamp signs. Dr. Gilbard describes his routine: "I look at the facial skin for telangiectasias and other signs of rosacea. I measure the palpebral fissure width to see how big a problem evaporation is. I look at the meibomian gland orifices to see if they are open, stenosed or closed and whether fluid comes out. I look at them from inside, everting the lower lid. Then, I brush the inferior tarsal conjunctiva with fluorescein.

"Decreased volume gives you decreased fluorescence and also de creased movement of the fluid after a blink," he continued. "You see debris in the tear film in advanced dry eye. In MGD, you see lots of fluorescence. The film looks watery and splashy. I look at the surface staining pattern. In a mild dry eye, there may be none. With insufficiency, the first stain you see will be the nasal bulbar conjunctiva because fresh fluid comes from the superior temporal aspect. By the same token, the temporal meniscus may fluoresce while the nasal meniscus does not."

Dr. Gilbard notes that with meibomianitis, the cornea and conjunctiva will stain initially along the lid margin. He also reports that staining with fluorescein and rose bengal will stain the cornea and conjunctiva equally in meibomianitis, unlike what happens in lacrimal insufficiency. This difference exists because the cornea and conjunctiva are equally susceptible, in Dr. Gilbard's experiments, to damage from inflammation, but damage from increasing osmolarity has an effect on the conjunctiva before the cornea.

Dr. Morier believes a problem with doctors and patients alike is that they think: "There's not much we can do; just use drops." He uses collagen plugs diagnostically, making sure the puncta are occluded, and gives the patients 2 weeks. This way, the patient gets the benefit of the plugs and then goes untreated again for several days. Then, the patient knows for certain if the plugs helped. He added that managed care pays very well for occluding puncta.

Dr. Morier likes the feeling he gets when a patient says, "I feel great. You fixed me."

"You want fewer complaints about contact lenses?" he asked. "Look at dry eye."

For Your Information:

Barbara Caffery, OD, MS, may be reached at 77 Bloor Street West, Suite 1409, Toronto, Ontario, Canada M5S 1M2; (416) 961-6671; fax: (416) 961-7958; e-mail: BCaffery@RUISSO.org.

Jeffrey P. Gilbard, MD, is medical director at The Cornea Center, clinical assistant professor at Harvard Medical School, clinical associate scientist at Schepens Eye Research Institute and president and CEO at Advanced Vision Research Inc. He may be reached at 7 Alfred St., Suite 330, Woburn, MA 01801; (800) 979-8327; fax: (781) 935-5075; e-mail: AVR@juno.com; Web site: www.theratears.com.

Frank J. Holly, PhD, director, may be reached at Dakryon Pharmaceuticals, 2579 S.S. Loop 289, Lubbock, TX 79423; (800) 658-2024 or (806) 745-2872; fax: (806) 745-2549. Dr. Holly has a financial interest in lissamine green. He is not a paid consultant for any company mentioned.

William D. Mathers, MD, may be reached at the Department of Ophthalmology, University of Iowa Hospitals, 200 Hawkins Dr., Iowa City, IA 52242-1091; (319) 356-2861; fax: (319) 256-0363; e-mail: William-Mathers@UIOWA.edu.

Albert Morier, OD, may be reached at the Lions Eye Institute, 35 Hackett, Albany, NY 12208; (518) 463-1211; fax: (518) 355-1208; e-mail: amorier1@nycap.rr.com. Dr. Morier has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Cristina M. Schnider, OD, MSc, director of professional relations and clinical affairs, Menicon USA Inc., can be reached at 333 W. Pontiac Way, Clovis, CA 93612; (209) 292-2020 or (800) 636-4268, ext. 114; fax: (209) 292-2021; e-mail: OD@MENICON.com.

Michael A. Lemp, MD, can be reached at University Ophthalmic Consulting of Washington, 4910 Mass. Ave., NW #210, Washington, DC 20016; (202) 686-6800; fax: (202) 686-6668. Dr. Lemp has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Susan E. Marren, OD, FAAO, may be reached at (609) 829-4229; e-mail: SMarren@aol.com. Dr. Marren has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned. Drs. Caffery and Mathers did not disclose whether or not they have a direct financial interest in the products mentioned in this article, or if they are paid consultants for any companies mentioned.

Lissamine green is available from Dakryon Pharmaceuticals, (800) 658-2024.

Zone Quick is available from Menicon USA, (800) MENICON.

For more information on the Model 3000 Nanoliter Osmometer contact Ken Micciche, product manager, Advanced Instruments, 2 Technology Way, Norwood, MA 02062; (800) 225-4034; fax: (781) 320-8181.

For more information about EagleVision's TearScope Plus Total Tear Film Kit call (800) 222-7584.