Eyeworld

EW FEATURE 50 Ocular surface disease • February 2016 AT A GLANCE • Optimizing the ocular surface prior to cataract surgery is critical to obtaining accurate readings. • Dry eye is challenging to treat because of the variation in signs and symptoms in patients. • Currently, Restasis is the only FDA approved treatment for dry eye disease. by Ellen Stodola EyeWorld Staff Writer Some newer study designs recog- nize some of the disconnect in dry eye disease and focus on including symptomatology and objective find- ings together in their measurements. Lifitegrast Dr. Hovanesian hopes that lifitegrast will be approved in 2016, but he said it would largely depend on the FDA's satisfaction with data that the company has submitted. The FDA previously reviewed phase 3 studies submitted by the company and gave a complete response letter several months ago but noted that they needed more data, as it could not be approved based on the trials submitted. The company, Dr. Hovanesian said, was already in the process of analyzing data from OPUS 3, which is a large, 711 patient phase 3 study looking at symptoms of dry eye. Shortly after receiving the complete response letter, Shire released posi- tive top-line data from the trial. The good news, he said, is that the data showed significant symptom im- provement at the target date, which was 3 months after treatment, and also at earlier time points at 14 and 4 days. "In other words, the product provides symptom improvement as dry eye, she said. Similarly, if you're looking at it from a symptomatic standpoint, that's also ambiguous. "If you're going to do a study to meet the endpoints and you're only looking at one or the other, you may not capture the true collective of dry eye disease patients," Dr. Yeu said. What is known about dry eye disease is a spectrum, she added, and there are going to be some patients who are extremely symptomatic with very little in terms of staining. What has changed since Restasis was approved? When Restasis was approved, the FDA didn't have a well worked out methodology for evaluating dry eye products, Dr. Hovanesian said. It's likely that by criteria used today, Restasis, in its original trial, may not have been approved, which is not to say that it's not an excellent product, he said. There are many products that would have excellent value that have not been approved because they can't overcome the hurdles, he added. Dr. Yeu said she's not sure if it's entirely because of the review process that Restasis is the only approved treatment. She thinks that the difficulty in identifying dry eye patients may also be a key factor. such as corneal staining, but are less symptomatic. This makes it very difficult to have a single study show improvement in both signs and symptoms, as the degree of dry eye signs and symptoms do not always correlate. "The objective criteria required to get approval has been an almost impossible hurdle to reach," Dr. Trattler said. "The FDA has very specific cri- teria it uses for approving products for dry eye involving improvement in both signs and symptoms," Dr. Hovanesian agreed. Physicians know that signs of dry eye can be quite variable among patients and can fluctuate based on factors that have little to do with medicine being used to treat the condition, he said. It's hard for companies to meet the FDA criteria, even with strong clinical impressions that the product is ef- fective. As a result of these stringent criteria, many products have fallen by the wayside, Dr. Hovanesian said. Many products have gone to trials and have not succeeded, Dr. Yeu said, adding that she thinks this could be due to the confusing nature of dry eye disease and how it can often be hard to make a diagnosis. If you look at it from an objec- tive standpoint and staining, it's hard to capture everyone who has Dry eye approved therapies today and in the future Experts discuss currently approved treatments for dry eye and other tactics they use to help treat these patients W ith only one FDA-ap- proved treatment for dry eye disease, help- ing these patients re- mains a challenge for physicians because of the volume of patients and variation in signs and symptoms of the condition. John Hovanesian, MD, Harvard Eye Associates, Laguna Hills, Calif.; Elizabeth Yeu, MD, Virginia Eye Consultants, Norfolk, Va.; and William Trattler, MD, Center for Excellence in Eye Care, Miami, discussed treatments currently approved and in the works for dry eye, how to optimize these patients prior to cataract surgery, and other factors. Currently, Restasis (cyclo- sporine, Allergan, Dublin) is the only approved product, but there is a lot of talk about lifitegrast (Shire, Lexington, Mass.), a product whose trials show promising results. Why is Restasis the only approved treatment? The availability of only a single pharmaceutical product to treat dry eye has a lot to do with the FDA's approval process and the clinical trial results required to receive approval. "It is obvious that the bar for dry eye medications to achieve FDA approval is set very high," Dr. Trattler said. One particular challenge with dry eye, he said, is that it's not as straightforward as it initially seems. There are some pa- tients who are highly symptomatic but show fewer signs of the disease, while others show significant signs, Lid margin debris cleaning with microblepharoexfoliation Source: Walter Fried, MD

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