Eyeworld

Supported by unrestricted educational grants from Allergan, Shire Pharmaceuticals, TearLab, and TearScience by Elizabeth Yeu, MD New and emerging therapeutics in dry eye disease New therapies help clinicians take aim at specific causes of dry eye W ith the range of therapies now available for ocular surface disease (OSD), clinicians can customize treatment, devel- oping targeted strategies based on its severity, cause, and signs and symptoms. Current options Approximately 80% of patients with dry eye have meibomian gland dysfunction (MGD); less than 10% of patients have purely aqueous deficient dry eye. Healthy meibomian gland function is foundational to ocular surface health. Optical coherence tomography with meibography allows us to examine the gland architecture and determine function. If meibum is good with some meibomian gland dropout, early aggressive treatment is im- portant because the clinician can reverse the disease process more readily than in a severe case. More customized lubricants are available, such as emulsions and emollient-friendly solutions to treat evaporative disease, and methylcellulose-based prepara- tions can be used for aqueous deficient disease. In addition, we will soon have omega-3 based artificial tears. From a nutritional stand- point, omega-3s, particularly triglyceride-based supplements, will be very important (Figures 1A and B). Vitamin A ointment, which is not available in the U.S., is helpful for keratinized lid margins and keratinized palpebral conjunctiva. Although warm compresses and lid massage are often recom- mended to manage lid margin disease, they can be detrimental and compliance may be a prob- lem. Lid scrubs with hypochlor- ous acid, commercial soap scrubs, and tea tree oil are also available, and many more effectively treat blepharitis. We can perform in-office lid margin cleansing, manual meibo- mian gland expression or thermal pulsation therapy, or microbleph- aroexfoliation. Cyclosporine 0.05% and lifitegrast are available as anti-in- flammatory treatments, as well as macrolides and tetracyclines, which can reduce MMP-9 levels, and topical corticosteroids, which usually are not used for chronic treatment. Many of my patients like the multi-dose cyclosporine 0.05% bottles, but single-dose vials are still available. Lifitegrast 5% is the first anti-inflammatory for dry eye approved by the U.S. Food and Drug Administration (FDA) to treat both signs and symptoms of dry eye. Onset of action occurs as early as 2 weeks, with greater reduction in dryness by week 6 and in inferior corneal staining at week 12. 1 Looking ahead A nasal neurostimulation device approved recently by the FDA can increase tear production and decrease dry eye symptoms. 2 In addition, new artificial tear formulations will be avail- able, as well as a cyclosporine 0.09% ophthalmic solution in a different type of vehicle com- pared with cyclosporine 0.05%. It has been shown to improve Schirmer's score in 12 weeks. Newer formulations of am- niotic membrane (AM) are on the horizon. What we do know is that AM improves corneal sensation and tear stability. 3 AM inhibits inflammation, and the presence of proteinase inhibitors may facilitate wound healing. 4 Several companies are working on AM drop formulations. I've been very pleased with my early experience with their amniotic cytokine ex- tract for my patients with dry eye. Different corticosteroid for- mulations such as an intracanalic- ular depot plug of dexamethasone has shown promise in treating OSD, in addition to lotepred- nol etabonate in a nanoparticle technology that penetrates tissues more readily. Cis-urocanic acid may serve as another anti-inflam- matory. Tavilermide, a naturally found protein that is being investigated, supports the cor- neal epithelium and nerves and helps induce mucin production. Researchers are also investigating SkQ1, an antioxidant reactive scavenger, and RGN-259, a thy- mosin beta-4 antagonist. Conclusion A range of treatment options are available to treat OSD, and more will be at our disposal within the next few years. They will help clinicians customize treatment, which should simplify the man- agement of dry eye disease. References 1. Semba CP, et al. Development of lifitegrast: a novel T-cell inhibitor for the treatment of dry eye disease. Clin Ophthal- mol. 2016;10:1083–94. 2. Friedman NJ, et al. A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease. Clin Ophthalmol. 2016;10:795–804. 3. Dogru M, et al. Corneal sensitivity and ocular surface changes following preserved amniotic membrane transplan- tation for nonhealing ulcers. Eye (Lond). 2003;17:139–48. 4. Hao Y, et al. Identification of antian- giogenic and antiinflammatory proteins in human amniotic membrane. Cornea. 2000;19:348–52. Dr. Yeu is assistant professor of ophthalmology, Eastern Virginia Medicine School, and is in private practice in Norfolk, Virginia. She can be contacted at eyeulin@gmail.com. Elizabeth Yeu, MD Figures 1A and B. Infrared meibography of the left lower lid taken 6 months apart in a 69-year-old woman who had MGD treatment with thermal pulsation and omega-3 fatty acid supplements. Notice the lid appears to have repopulation of the meibomian glands inferiorly where there was great disorganization of architecture originally. 5

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