DRY EYE UPDATE
DRY EYE UPDATE
Part I of this two-part series highlights new research and products.
By Barbara Caffery, O.D. Toronto, Canada

As eyecare practitioners, you probably know that an estimated 59 million Americans suffer from dry eye. You're also most likely aware that dry eye syndrome has many causes, ranging from the normal aging process to environmental conditions to computer work and contact lens wear. In fact, because so many people experience dry eye symptoms and because so many factors come into play with this syndrome, it's one of the most common problems you treat.

With this in mind, it's only logical that you need to become aware of all the treatment options available. In this update, we'll let you know what's going on around you in the area of dry eye. First we'll take a look at some areas of research from the past year, then we'll review some of the newer products on the market.

We'll come back again in April with Part II, which will include punctal occlusion questions answered by an expert, an interesting proposed method to treat dry eye, highlights from the first clinical conference on Sj�gren's syndrome and much more.

Dry Eye Research

A look at some exciting new research from the past year.

Dry eye is an area of interest for a growing number of researchers. Let's look at some of the more interesting research findings reported in 2000.

Although many of these concepts are unproven, it's important to keep abreast of the latest thinking in this area. They'll change our concepts of many diseases and improve our treatment tactics.

• The neurological control of conjunctival goblet cells in rats. Darlene Dartt, Ph.D., presented this paper at last year's Association for Research in Vision and Ophthalmology (ARVO) meeting. Goblet cells manufacture mucin sacs that travel to the cell membrane and explode into the tear film, releasing all the granules from the cell. Dr. Dartt explored the role of the nervous system in controlling goblet cell function. She theorized that when the cornea is irritated by dry eye, sensory information to the central nervous system produces efferent messages to the ocular surface goblet cells in a form of feedback loop.
  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, minimal stimulation of the cornea and conjunctiva produces mild parasympathetic stimuli for regular goblet cell secretions. Corneal damage associated with severe or prolonged dry eye results in decreased sensitivity.
  With lessened stimulation, the eyes become drier, which causes more damage and further reduced sensitivity. Severe Sj�gren's syndrome is an example of this extreme. Also, with giant papillary conjunctivitis (GPC), the cornea is continually irritated, which in turn causes more mucus secretion.
• A lacrimal gland and tear film conference was held in Hawaii in November. The Dry Eye Investigations (DREI) group reported on their research questioning subjects about their ocular surface symptoms. They asked the volunteers, "When it comes to the feelings on the surface of your eye, what do you feel, how badly do you feel it and when do you feel it the most?"
  The most common feeling of both contact lens wearers and non-wearers was discomfort. Contact lens wearers felt the symptom of dryness more often and more intensely than the non-lens wearers. Most subjects with symptoms felt the sensations more intensely in the evening.
  This diurnal variation is important for clinicians to note as they may wish to see their patients later in the day or ask them about their symptoms later in the day to weed out those who have true dry eye.
• At last year's ARVO meeting, Michael Stern, Ph.D., of Allergan Pharmaceuticals, described dry eye disease as a local inflammatory process. Levels of androgens, steroid hormones that protect the ocular surface from inflammation, decrease with age. When the level is reduced as in menopause, ocular cells make more cytokines that attract T cells to the conjunctiva, producing surface damage and increased symptoms of dry eye disease.
  Dysfunction occurs in the salivary and lacrimal glands early in Sj�gren's syndrome. Programmed cell death occurs, allowing an influx of lymphocytes into these glands, resulting in damage and reduced function.
• Also at last year's ARVO meeting, Stephen Pfluegfelder, M.D., discussed inflammatory changes on the ocular surfaces of dry eye patients. Compounds in normal tear film, including lactoferrin, TLMP IL-1 and TGBF, reduce inflammation. Lactoferrin was significantly reduced in the tear film of Sjogren's syndrome subjects.
• Restasis study. Another lecture at ARVO 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.
  • The European research results on the Restasis (cyclo-sporine 0.05%) study showed decreased symptoms and improved ocular surface conditions in patients using the topical cyclosporine. Interestingly, the vehicle alone improved many sit- uations, suggesting that both the placebo effect and rigorous use of drops can help many patients.
    Final FDA clearance for Restasis awaits additional information from the manufacturer and further FDA review because the company needs to conduct another confirmatory study. Allergan, Inc., manufacturer of the drug, is seeking an indication for the topical treatment of moderate to severe dry eye.
• Risk factors. The September 2000 issue of Archives of Ophthalmology reported the study findings of researchers from the University of Wisconsin Medical School in Madison. In the study of 3,703 individuals ages 48 to 91, 534 of them reported symptoms of dry eye syndrome in the past 3 months or longer.
  Current smokers were 82% more likely than nonsmokers to have dry eyes and former smokers were 22% more likely to have dry eyes than nonsmokers.
  Participants who consumed caffeine, mostly through coffee, were found to be 25% less likely to have dry eyes. The researchers noted that compounds known as xanthines (caffeine is one of them) have been shown to stimulate tear production when applied topically. However, it's not known whether ingested caffeine has a similar stimulatory effect.
  The study results suggest that several factors, such as smoking, caffeine use and multivitamin use, could be studied for preventative or therapeutic efficacy.

Dr. Caffery practices in a group setting in Toronto, Canada. Her practice is dedicated to contact lenses and dry eye research.

New Product Overview
Here's a quick look at some of the new dry eye products that are available and those that are on the way.

Moisture chamber

Here's a way to help your patients with moderate to severe dry eyes retain the available moisture on their eyes. Curtailing the rate of moisture evaporation is of particular value when the patient lives in arid or windy areas. EagleVision Moist Eye Moisture Panels can be fitted to most any configuration of eyewear, between the lens and frame, to create a moisture chamber around each eye.

For additional information, contact the company at (800) 222-7584 or visit www.eaglevis.com.

Nutritional products

• You know that many patients suffer from dry eyes following laser vision correction surgery. Well, ScienceBased Health has unveiled a new approach to alleviate side effects and speed healing of post-surgical dry eye. KeraCaps Complex is an oral nutritional product that combines omega fatty acids to help restore natural eye moisture and other specific eye health factors.
  KeraCaps Complex is a combination of the formulations HydroEye and OcularEssentials by ScienceBased Health.
• ScienceBased Health's HydroEye is a proprietary blend of omega-6 fatty acids, mucin complex and nutrient cofactors that addresses the root causes of dry eye syndrome. According to the makers, HydroEye helps prevent drying and atrophy of the tear glands while supporting proper tear secretion by promoting the normal structure and function of the lacrimal glands, conjunctival goblet cells and the mucin network.
  For additional information on either of these products, contact ScienceBased Health at (888) 433-4726 or www.sciencebasedhealth.com.
• Carlson Laboratories, Inc. has a product called Moistur-Eyes. It contains the nutrients documented to be helpful in improving tear quality, including Vitamins A, C, B₆ and the essential fatty acids EPA, DHA and GLA.
  Call (888) 234-5656 or visit www.carlsonlabs.com for details.

In-office tear analysis

Touch Scientific, Inc. manufactures the Touch Tear MicroAssay System, an in-office method of molecular tear analysis. The information is helpful for separating dry eye into specific etiologies.

Specific tests include lactoferrin (reimbursed under CPT code 83520) and IgE (reimbursed under CPT code 82785) for determining "at risk" patients for giant papillary conjunctivitis and other allergic responses.

The average test reimbursement is $25, and it costs you less than $10. The system is designed to use all future tests, including Gram-positive and negative, HSV Adenovirus and long-term hypoxia. You can lease it for about $299 per month.

For more information, call (919) 872-4445 or visit www.touchscientific.com.

Lubricant gel

Cynacon/Ocusoft recently introduced Tears Again Gel-Drops, a lower viscosity alternative to the company's Tears Again Night & Day Lubricant Gel. It's the same water-based formula as the Night & Day version, but the Gel-Drops have half the viscosity. It comes in a 15-ml dropper bottle and lasts 4 to 6 hours. Patients use one drop in the morning and one in the evening.

For samples or more information, call (800) 233-5469 or visit www.ocusoft.com.

In the pipeline

Inspire Pharmaceuticals, Inc. has initiated the Phase III clinical program for the P2Y (2) receptor agonist INS365 Ophthalmic for the treatment of dry eye in the United States.

INS365 Ophthalmic is a small-molecule drug that stimulates the P2Y (2) receptor, a key mediator of mucosal-surface hydration and lubrication.

Based on the results from the Phase II program, the company expects this new approach to enhance the eye's natural cleansing and protective systems by stimulating the release of salt, water, mucus and other natural tear components, providing hydration and lubrication of the ocular surface.

The Phase III program consists of two pivotal clinical trials designed to enroll a total of approximately 1,000 patients with dry eye in 60 ophthalmology centers.

Both studies are double-masked comparisons of two concentrations of INS365 Ophthalmic and a placebo to evaluate the efficacy of the product on a chronic basis. Both objective ocular-surface measurements and subjective assessments have been incorporated into the study design, based on discussions with the FDA.

The company has target dates for its new drug, but they aren't set in stone. It hopes to finish the Phase III program in the first half of 2002 and to file a new drug application (NDA) in the second half of 2002. It's also looking to launch INS365 Ophthalmic in mid-2003.

The company has entered into a development and commercialization alliance with Santen Pharmaceutical Co. Ltd. for this product.

For more information, call (919) 941-9777 or visit www.inspirepharm.com.