APR 2013

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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46 EW FEATURE February 2011 Dry eye/ocular surface April 2013 Promising dry eye therapeutics by Michelle Dalton EyeWorld Contributing Writer AT A GLANCE • Several new therapeutics in development for dry eye work on a different aspect of the disease than topical cyclosporine 0.05%. • Lifitegrast—a T-cell immunomodulator—may be the closest to being filed for regulatory approval. • An iontophoresis system is showing therapeutic value, but may be too cumbersome to gain market support for mild dry eye. • Nanotechnology may hold the most potential as it promises better bioavailability than current eye drops. With any luck, clinicians will soon have more options for treating dry eye Note: This article discusses compounds that are investigational and not yet approved in the U.S. F or more than a decade, clinicians have had only one therapeutic approved for the treatment of dry eye, although several others have gone through the clinical trial process only to fail in improving both clinical signs and objective symptoms. "We have come to the realization that managing dry eye is one of the most important opportunities for ophthalmologists—and doing so improves almost all outcomes in cataract and refractive surgery," said Eric D. Donnenfeld, MD, partner, Ophthalmic Consultants of Long Island, Rockville Centre, N.Y., and clinical professor of ophthalmology, NYU medical school, New York. Robert Latkany, MD, director, Physician EyeCare of N.Y., New York, has been telling patients for years "something may be coming out shortly, but unfortunately it has become a lot more challenging to get regulatory approval." With so many new therapeutics heading into later stage development, though, he remains optimistic one or more may gain approval. The majority of products in development "are either trying to reduce inflammation or trying to enhance aqueous production," said Richard L. Lindstrom, MD, founder, Minnesota Eye Consultants, Minneapolis. With "probably 20 dry eye medications in the pipeline and only a handful likely seeing the light of day in the next few years, both clinicians and patients are understandably frustrated," said Vincent P. de Luise, MD, assistant clinical professor of ophthalmology, Yale University School of Medicine, New Haven, Conn. "Dry eye is so common and multifactorial, the more things we can have in our arsenal, the better off we are," said Jay Pepose, MD, founder and medical director, Pepose Vision Institute, Chesterfield, Mo., and professor of clinical ophthalmology, Washington University School of Medicine, St. Louis. "To get a product through the FDA, we need to improve some aspect of both the patients' signs and symptoms—whether it's increasing goblet cell density or helping produce more mucin, or maybe it's something coupled with the newer secretagogues to improve the lipid layers." cause—or causes to a lesser extent— the intraocular pressure spikes other steroids do. Other cyclosporine products—a 0.5% and a 0.1% version—all have to overcome the stinging that occurs with instillation, Dr. Latkany said. "These subgroups of the cyclosporine product already in existence are probably closest to approval," he said. "If they can overcome the stinging, these products may be a step up from the 0.05% version currently marketed." Here, a rundown on some other promising therapeutics. CF-101 CF-101 is an anti-inflammatory steroid that is a first-in-class small molecule targeting the A3 adenosine receptor, Dr. de Luise said. Through an 82% holding in OphthaliX (Carson City, Nev.), developer Can-Fite (Petah-Tikva, Israel) is investigating the compound for dry eye (phase 3 in Europe, Israel, and the U.S.) and glaucoma (phase 2 in Europe and the U.S.). "It's an oral medication, though, and it's easier to get ocular medicines into the eye through localized methods such as drops or injections rather than systemically," Dr. de Luise said. EGP-437 This compound is a corticosteroid solution tailored for iontophoresis, The topical cyclosporine factor Topical cyclosporine 0.05% only works on newly formed T-cells. Since T-cells live about 110 days, a response in two to three weeks is unrealistic, Dr. de Luise said. "Currently circulating T-cells are unaffected by topical cyclosporine, and it's not until the new T-cells, the ones that haven't yet been activated by the inflammatory process that can be inhibited by the medication, are born that patients will see an effect," he said. Some clinicians are now prescribing short courses of loteprednol in conjunction with topical cyclosporine 0.05%, Dr. Lindstrom said. The glycerol and propylene glycol "are two very good lubricants similar to those used in artificial tears, so very surface-friendly," he said. A "soft steroid," loteprednol is one adjunctive drug that "makes topical cyclosporine appear to act 'faster'—but it's really the steroid that's giving the patient the shortterm relief," Dr. de Luise said. Additionally, Dr. Donnenfeld said loteprednol, a gel that "sticks" to the surface, does not seem to Clumped central corneal staining with fluorescein is seen in a patient with dry eye and complaints of fluctuating, ghosty vision. Inferior staining of the cornea and bulbar conjunctiva with rose bengal is seen in this patient with dry eye. Source (all): Jay S. Pepose, MD

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