Medications for Dry Eye
Artificial tear preparations (demulcents and emollients) form an occlusive film over the corneal surface to lubricate and protect the eye from drying. The active ingredients in demulcent preparations are polyvinyl alcohol, cellulose, and methylcellulose as well as their derivatives: hydroxypropyl cellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, and carboxymethylcellulose. Other ingredients used include glycerin, polysorbate 80, polyethylene glycol 400, dextran 70, povidone, and propylene glycol.
The viscosity of artificial tears varies in part because of the concentration of the wetting agent. For example, carboxymethylcellulose is available in 0.25%, 0.5%, and 1% solutions; higher-viscosity solutions are used to treat increasingly severe dry eye symptoms.
Some data support the hypothesis that changes in tear osmolality trigger corneal and conjunctival epithelial damage and initiation of dry eye. Artificial tear products with lower osmolality may relieve dry eye symptoms to a greater extent, but clinical results thus far have not been conclusive.
The pH of commercially available artificial tear products also varies widely. A patient may experience a stinging sensation after eyedrop use because of a mismatch between the pH of the instilled eyedrops and that of the patient’s tear. Patients who report a stinging sensation following eyedrop use can try another product with a different pH.
Multidose preparations also contain preservatives, including benzalkonium chloride, EDTA (ethylenediaminetetraacetic acid), methylparaben, polyquad (polyquaternium 1), potassium sorbate, propylparaben, sodium chlorite, sodium perborate, and sorbic acid. Although early preservatives such as thimerosal and benzalkonium chloride were highly toxic, the newest generation of ophthalmic preservatives are less harmful to the ocular surface. Nonpreserved unit-dose preparations eliminate the cytotoxic effects of preservatives.
Ocular emollients are ointments prepared with sterile petrolatum, liquid lanolin, mineral oil, methylparaben, and polyparaben. Ophthalmic lubricating ointments help ease the symptoms of severe dry eye and exposure keratopathy and are suitable for nighttime use in dry eye and nocturnal lagophthalmos.
Topical cyclosporine emulsion, 0.05%, targets the inflammatory etiology of dry eye. Because cyclosporine is poorly water soluble, it is prepared in an emulsion composed of glycerin, castor oil, and polysorbate 80. It is available in a multidose bottle and a preservative-free single-use package. The oily vector is marketed separately as a tear supplement. Studies have shown that twice-daily dosing with this drug has negligible systemic absorption and adverse effects. Biopsies have demonstrated a measurable repopulation of goblet cells and a decrease in both conjunctival epithelial cell turnover and the number of lymphocytes. Lifitegrast, 5%, preservative-free topical solution, a lymphocyte function–associated antigen 1 (LFA-1) antagonist administered twice daily, was approved by the FDA in 2016 for treatment of dry eye. It inhibits binding of intercellular adhesion molecule-1 (ICAM-1) to LFA-1 and has been effective in reducing ocular surface inflammation.
Given the wide variety of commercially available products, some principles can help guide the selection of artificial tear preparation for a particular patient. Generally, a more viscous tear lubricant should be used as the severity of the dry eye increases. A trial-and-error approach that involves titration of the frequency of instillation according to the patient’s daily activities, the use of tear substitutes with different mechanisms of action or properties, and even a combination of different lubricants may be necessary. Preservative-free products should be utilized if frequent instillation is required, such as for severe dry eye. Nonpreserved preparations are at risk of microbial contamination and therefore should be discarded within a few hours of use, even though the vial may be recapped after opening.
For the treatment of ocular surface diseases such as persistent epithelial defects, superior limbic keratoconjunctivitis, keratoconjunctivitis sicca, and neurotrophic keratopathy, autologous serum eyedrops are beneficial. They are formulated by compounding a 20% solution packaged into sterile dropper bottles. Reported complications include peripheral corneal infiltrate and ulcer, eyelid eczema, microbial keratitis, ocular discomfort or epitheliopathy, bacterial conjunctivitis, scleral vasculitis and melting in patients with rheumatoid arthritis, and immune complex deposition with 100% serum.
Two dry eye products currently under investigation are diquafosol tetrasodium and rebamipide. Diquafosol tetrasodium is a P2Y2 purinergic receptor agonist that activates P2Y2 receptors on the ocular surface, causing rehydration through activation of the fluid pump mechanism of the accessory lacrimal glands on the conjunctival surface. It was approved for use in Japan in 2010 for treating dry eye. Rebamipide is a derivative of quinolone-class antibiotics that enhances the secretion of mucin to support tear film adhesion and slow tear film breakup time (also see BCSC Section 8, External Disease and Cornea).
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Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.