by Lisa B. Samalonis Contributing Editor

N ew research sheds light on the mechanisms of dry eyes and gives clues on how to treat them effectively. According to the National Institute of Health, dry eye is a disorder of the tear film due to tear deficiency or excessive evaporation, which causes damage to the interpalprebral ocular surface and is associated with symptoms of ocular discomfort. Various types of dry eye include mucin deficient, aqueous deficient (keratoconjunctivitis sicca), or evaporative. "There are some dry-eye patients who have low-water tear production, and they are called aqueous tear deficient," said Stephen C. Pflugfelder, MD, professor, Cullen Eye Institute, Baylor College of Medicine. "Another group has adequate tear production, but they have an unstable tear film or a lipid tear deficiency due to a disease such as meibomian gland dysfunction. Finally, there are those patients who may also develop an aqueous deficiency due to increased evaporation or more rapid blinking."

Aqueous-deficient dry-eye disease

Accumulating evidence suggests that aqueous-deficient dry-eye disease results from localized immune-mediated inflammatory processes that ultimately affect the entire ocular surface/lacrimal gland/neural feedback functional unit, said Henry D. Perry, MD, associate clinical professor, Cornell University Medical College, New York City. "The main and accessory lacrimal glands may be made susceptible to inflammation due to degenerative processes resulting from a decrease in neural or androgen support.

The degenerative processes trigger chemically mediated inflammation that leads to activation of trafficking lymphocytes [T-cells]. In turn, the activation of lymphocytes leads to T-cell-mediated inflammation, cytokine production, the presence of cytokines in tears, and acinar cell apoptosis," said Perry, who is in practice in Rockville Centre.Research has shown that cytokines in tears trigger T-cell-mediated inflammation on the ocular surface, disrupt epithelial cell function, interfere with mucin production, and decrease corneal sensitivity by a direct effect on sensory neurons and by thickening of the ocular surface epithelia.

Recent evidence has shown that creating a laser in-situ keratomileusis flap produces a neurotrophic cornea, which results from trauma or corneal exposure following trauma to corneal nerves. This is often accompanied by loss of corneal sensitivity. "Corneal hypesthesia can lead to ocular surface disease manifested as a significant epitheliopathy," said Frank A. Bucci Jr., MD, in private practice in Wilkes Barre, Pa. "Patients with pre-existing ocular surface disease, such as meibomian gland dysfunction, frank keratoconjunctivitis sicca, chronic allergic conjunctivitis, or borderline dry-eye disease are at the greatest risk of developing epitheliopathy post-LASIK," he said. "Epithelial defects from the microkeratome pass can lead to chronic ocular surface problems, especially in patients with anterior basement membrane dystrophy."

Pflugfelder said that although ophthalmologists go through a dry-eye algorithm for treating LASIK dry-eye patients, they don't always respond as well as conventional dry-eye patients.

In order to choose from the wide range of options, he advised that ophthalmologists create a step-by-step approach. "For a vast majority of dry-eye patients, artificial tears will work. For those with aqueous tear deficiency, punctal plugs could be considered," he said.

Many lubricants are available, including artificial tears, tears with disappearing preservatives, and multidose preserved artificial tears. "We do know that preservatives are toxic and people who use the tears more than four times a day should consider a nonpreserved tears," Pflugfelder said.

Pflugfelder said that several types of beneficial, rapidly disappearing gels are now on the market. "These gels don't tend to blur vision as much as ointments," he said. "In addition, the patients prefer the gels to ointments because they are easy to use. Most ointments are reserved now for people to use at bedtime or if they have severe dry eye, where their lids don't close and they are beginning to form ulcers."

For patients with moderate to severe dry eyes, new gels - more viscous than drops but not as heavy as ointments - can provide some needed relief.

Two available gel formulations include Tears Again® Gel Drops™ and Tears Again® Night and Day Lubricant Gel (carboxymethylcellulose sodium, CYNACON/OCuSOFT). The drops are available in 15-mL dropper bottles and are half the viscosity of the gel. Both can be used throughout the day or night. These gel formulations are water-based and are said to last for 4 to 6 hours.

Bucci conducted a study to evaluate the effects of silicone punctal plugs on tear lactoferrin levels following LASIK. He found that the neurotrophic cornea created by the LASIK flap resulted in a statistically significant decrease in tear lactoferrin levels within 1 day in unplugged eyes. He also found that the use of the silicone punctal plugs in the lower lid eliminated a significant decrease in tear lactoferrin levels at 1 day post-LASIK.

In addition, the significant difference in tear lactoferrin levels between plugged and unplugged eyes appears to persist for up to 6 months following LASIK. "This data suggest that the placement of silicone punctal plugs following LASIK positively impacts the ocular surface," Bucci said.

Bucci reported that the mean tear lactoferrin level for all eyes decreased 15% in the study 1 day following LASIK. Tear lactoferrin decreased 22% in unplugged eyes and only 9% in plugged eyes. Two hundred and seventeen bilateral observations of lactoferrin were obtained for the entire study and tear lactoferrin levels in plugged eyes were significantly greater than in unplugged eyes. The mean lactoferrin level for plugged eyes was greater at all follow-up visits.

Contact Information
Bucci: 570-825-5949, fax 570-825-2645
Perry: 516-766-2519, fax 516-678-7377
Pflugfelder: 713-798-4732, fax 713-798-1457