Eyeworld

EW CORNEA 64 February 2016 by Maxine Lipner EyeWorld Senior Contributing Writer be cured," Dr. Pflugfelder said. "But in a patient who has plenty of tears and doesn't have any loss of goblet cells, in my experience the response to it is low." Dr. Yeu agreed that Restasis positively affects the lacrimal gland in producing aqueous. She pointed out that practitioners have learned through experience that because it is a T-cell inhibitor that prevents the activation of T-cells, it can take some time to get all of these out of circulation. However, once this does occur, there can be myriad improve- ments over time. "We do over time improve the tear film, and this is go- ing to have a positive effect on the lid margins," Dr. Yeu said. "That has been shown to be beneficial in even atopic allergic conjunctivitis because it is higher along the (inflammatory) cascade." It can also be used to augment treatment in blepharitis and lid margin disease. It is the role of immunomodu- lators to either suppress the migra- tion of the T-cells onto the eye or to block the production of cytokines by these T-cells, he explained. The drug lifitegrast does the former, while Restasis does the latter. In his experience, those with aqueous tear deficiency do well with Restasis. These are patients whose lacrimal gland doesn't work well and have a low level of tears on their eyes, Dr. Pflugfelder noted. "That's the group that has the highest number of T-cells and the highest level of certain cytokines that are produced by T-cells," he said. "It makes sense that Restasis would work well in those eyes." These are also the eyes that have the greatest amount of goblet cell loss. "If I see a patient who has aqueous deficiency and a fair amount of dye staining on their eye, I can almost guarantee that they'll respond well to Restasis and in some cases even potentially immunomodulators that block the top of that inflammation cascade by blocking phospholipase, Dr. Yeu said. Stephen C. Pflugfelder, MD, professor of ophthalmology, Bay- lor College of Medicine, Houston, likewise views immunomodulation as playing a key role in dry eye, with Restasis serving an important function here. "If the lacrimal gland is not working and people have less water in their eyes, T-cells come onto the eye and they start making factors," Dr. Pflugfelder said, add- ing that these start producing more cytokines. When that happens, the goblet cells that produce mucus start to vanish and in the worst cases disappear completely, with the eye not faring well. "I think it's now recognized that the goblet cells are key cells that can maintain health and minimize inflammation on the surface of the eye," Dr. Pflugfelder said. Experts discuss 2 immune modulators to help alleviate dry eye disease D ry eye disease affects 25–30 million Americans, according to Elizabeth Yeu, MD, partner, Virgin- ia Eye Consultants, and assistant professor, Eastern Virginia Medical School, Norfolk, Va. While many reach for artificial tears for treatment, this condition may be more suited to an immunomod- ulatory approach. In a significant amount of cases, there's a cycle of inflammation, and that inflammato- ry cascade can be positively targeted to help halt the process, Dr. Yeu explained. EyeWorld took a closer look at what immune modulators such as Restasis (cyclosporine, Aller- gan, Dublin) and lifitegrast (Shire, Lexington, Mass) have to offer. Why use immune modulators The rationale for using immune modulators is clear-cut. "We can treat and reverse the severity of dry eye disease or stabilize this by halting the inflammation," Dr. Yeu explained, adding that otherwise this can become a vicious cycle. "Once the inflammation is present in the tear film, this leads to damage not only to the lacrimal gland but also to the actual surface, including the lid margin," she said. "Whatever the cause was to begin with, it often ends up being a mixed etiology picture, especially as the disease pro- gresses." With this in mind, the idea is to keep the tear film as healthy as possible by modulating the inflam- matory cascade and mitigating it. This will then create a healthier sur- face and reverse any changes there. This helps explain why cyc- losporine often works to improve Schirmer's scores in dry eye cases, she said. "By mitigating the inflam- mation, it improves the health of the lacrimal gland, which is then able to function more appropri- ately in aqueous production," Dr. Yeu said, adding that there are different immunomodulators in development, with one close to FDA approval. In addition, this is why steroids work so well—steroids are Treatment management with immunomodulation Severe corneal fluorescein staining and filamentary keratitis in a patient with aqueous tear deficiency Source: Stephen Pflugfelder, MD Pharmaceutical focus

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