EyeWorld Asia-Pacific June 2014 Issue

June 2014 59 EWAP PHARMACEUTICALS Lissamine green (LG) staining of the conjunctiva in a patient with mild dry eye. LG is a valuable vital dye to use because it is very sensitive and highlights even early devitalization of conjunctival epithelium. Fluorescein staining of a cornea in a patient with moderate dry eye. Broken tear film over the central cornea (decreased tear film break-up time) and fluorescein staining of the inferior cornea. Fluorescein stains epithelial cells in more advanced disease, as well as absent areas (erosions) on the corneal surface. Source: Vincent P. de Luise, MD A clear-eyed view of preservatives in tears by Maxine Lipner EyeWorld Senior Contributing Writer Taking the sting out for patients U sing artificial tears is a fact of life for many patients with dry eye disease, according to Vincent P. de Luise, MD , assistant clinical professor of ophthalmology, Yale University School of Medicine, New Haven, Conn., U.S. Debra Schaumberg, ScD, OD, from the Harvard School of Public Health, has reported that between 25 and 40 million Americans have some level of dry eye, Dr. de Luise said, and virtually all of these patients are using artificial tears, if not daily then certainly during their week. With preservatives in many such tears on the drugstore shelves, EyeWorld asked leading practitioners to take a closer look at these and at potential alternatives for dry eye patients. Dr. de Luise noted that practitioners can offer patients some environmental strategies for keeping the ocular surface moist. For example, they can suggest putting a cold mist humidifier near the computer. Blink rates dramatically decrease and tears evaporate more rapidly during computer use, and a humidifier can be very helpful. Another useful recommendation is placing a pillow on the desk chair. “Sitting on a pillow raises your body an inch or two, resulting in the upper lid lowering about 1 mm as the patient is now looking down a tiny bit on the computer screen,” Dr. de Luise said. “Lowering the upper eyelid about 1 mm covers the cornea 1 mm and thus reduces evaporation up to 15%.” Still, use of artificial tears looms as the next step in the treatment of most patients. Both the FDA and the U.S. Pharmacopeia mandate use of preservatives for nearly all ophthalmic drops in bottles or multidose vials. Such eye drops have active ingredients as well as inactive ingredients, the latter of which are called “excipients.” Dr. de Luise described excipients as including the preservatives, the buffers that keep the PH of the eye drop within a certain range, and viscosity agents that help increase the contact time of the eye drop on the ocular surface. “The more inactive ingredients in an eye drop, the more worried I get as far as patient comfort and ocular toxicity are concerned,” Dr. de Luise said. “Over the decades of managing dry eye patients, I have preferred going immediately to non-preserved tears.” Preservative types There are two major types of preservatives to consider— chemical and oxidative. “Chemical preservatives are older science, tend to be more irritating and toxic to the conjunctiva and corneal epithelium, but are still found in many bottled artificial tear drops,” Dr. de Luise said. “Oxidative preservatives are newer science, less toxic, and thus friendlier to the surface of the eye, but they’re still preservatives and still have some toxicity.” Chemical preservatives in tears include benzalkonium chloride (BAK) and chlorobutanol. Of the two, Dr. de Luise observed, the latter is considered friendlier to the ocular surface. “Chlorobutanol is an alcohol-based chemical preservative,” he said. “It works by disorganizing the lipid structure of the microbial cell membrane and thereby increasing its permeability—the cell loses salt, potassium and sodium, other molecules ingress, and the cell is destroyed that way.” BAK is a cationic surfactant quaternary ammonium detergent and works by breaking open cell membranes, lysing the cytoplasm, and destroying intracellular structures, Dr. de Luise explained. Other chemical preservatives include sorbate, which has been around for decades, and Polyquad, which is a newer and much gentler quaternary ammonium preservative. Polyquad is found in Tears Natural II (Alcon, Fort Worth, Texas, U.S.) and in some contact lens solutions. “Polyquad is less toxic to the corneal and conjunctival epithelium, which means it is friendlier to the surface of the eye,” Dr. de Luise said. “Yet after studying and using these agents for three decades, it remains evident that all chemical preservatives have some degree of toxicity to the corneal and conjunctival epithelium.” Dr. de Luise views oxidative preservatives as newer science with the advantage of less ocular surface toxicity. Sodium perborate is one such oxidative preservative. It is sometimes nicknamed a “vanishing preservative” because the sodium perborate rapidly decomposes into hydrogen peroxide, which ultimately breaks down into salt and water. GenTeal (Novartis, Basel, Switzerland) is one artificial tear that contains sodium perborate, Dr. de Luise said. continued on page 60