Eyeworld

EW CORNEA 38 August 2016 by Liz Hillman EyeWorld Staff Writer New biomarker and possible treatment target for difficult to diagnose autoimmune disease M ultiple scientific studies estimate that between 1 million and 4 million people in the U.S. have Sjögren's syndrome. Part of the reason for this large range in prevalence of the autoimmune disease, which is characterized by in- flammation and dysfunction of the lacrimal and salivary glands, among other things, could be because the condition is so difficult to diagnose. Sarah Hamm-Alvarez, PhD, vice chair of basic research, and profes- sor of ophthalmology, University of Southern California Roski Eye Institute, Los Angeles, said when she first started Sjögren's research, it took between five and seven years to diagnose a patient. Now, it takes an average of 3.5 years, according to the Sjögren's Syndrome Foundation. But even that time frame can lead to debilitating disease progres- sion that clinicians think could be prevented if diagnosed and ad- dressed earlier. There is no single test to confirm a Sjögren's diagnosis; it is usually driven by a rheumatologist who considers salivary and gland function along with other physically observed symptoms and blood and ocular tests. Recent research has identified a possible new biomarker that could potentially serve as an early diag- nostic tool. Researchers also drilled down further into the mechanism behind this biomarker to under- stand a potential treatment pathway that could target dry eye symptoms unique to Sjögren's patients. Searching for early diagnostic biomarkers A couple of years ago, Dr. Hamm- Alvarez and her colleagues published a paper on research announcing they had found the activity of the protein cathepsin S is "significantly enhanced" in the tears of Sjögren's patients compared to non-Sjögren's, dry eye patients or those with other autoimmune diseases. 1 This group has identified other tear biomarkers of disease as well, but none, Dr. Hamm-Alvarez said, are substitutes for cathepsin S. "Cathepsin S is the single most powerful indicator of disease status," she said, explaining that she and her colleagues are speaking with numer- ous companies about the potential to develop a tear test for the protein. "What we know from our studies in disease model mice is that tear cathepsin S is elevated early and continues to rise as disease advances, so we do think it could be an early indicator of the inflammation of the lacrimal gland," Dr. Hamm-Alvarez said. Several blood biomarkers have been identified as having early diag- nostic potential for Sjögren's as well, said Penny Asbell, MD, director of cornea and refractive services, Icahn School of Medicine at Mount Sinai, New York. One test, the Sjö Diagnostic Test (Bausch + Lomb, Bridgewater, New Jersey), includes four traditional biomarkers as well as three novel, proprietary biomark- ers to help detect early Sjögren's syndrome. "There is definitely a hunt in looking for the right biomarker that would be diagnostic, not just for Sjögren's syndrome but for other types of dry eye as well, and one Research identifies powerful indicator of Sjögren's syndrome state duration of effect for the ther- mal devices. When a patient presents with red and puffy lids that are stuck together and complains about burn- ing or irritation, Dr. Sheppard said clinicians should be concentrating on getting dynamic meibomian im- aging. He prefers to use the LipiFlow and LipiView or the 5M Keratograph (Oculus, Wetzlar, Germany), which combines keratometric and corne- al topography measurements and includes robust dry eye screening software. "Those 2 devices are game changers. When you evaluate those pictures with patients, it's amazing how patients buy in and under- stand. They intrinsically understand we're not going to get them 100% back, but there is a heightened sense of prioritization to do their part to preserve their existing glands," he said. He's also a firm believer in per- forming an allergy skin test. "Know- ing if they respond to histamine and to what degree can be invaluable when we're treating dry eye," he said. Incorporating into practice These diagnostic tools "have the unique ability to motivate the lid disease patient to move forward. Because the LipiFlow is a therapy that can be performed in office, it's created a 94% satisfaction rate in our practice," Dr. Sheppard said. Dr. Pflugfelder suggested before committing to any one specific diag- nostic or treatment tool, clinicians weigh the fees associated. Some procedures are in-office and can be performed by either technicians or physicians. Some business models dictate physicians buy the instru- ment but are free to set their own prices. Other business models dictate physicians purchase individual treat- ment packs, which can elevate out- of-pocket costs for the patient. EW Editors' note: Dr. Pflugfelder has no financial interests related to his comments. Dr. Sheppard has finan- cial interests with Alcon (Fort Worth, Texas), Aldeyra Therapeutics (Lexing- ton, Massachusetts), Allergan (Dublin), Bausch + Lomb (Bridgewater, New Jer- sey), LacriScience, Paragon (Baltimore), Parion (Durham, North Carolina), Rapid Pathogen Screening, ScienceBased Health (Houston), Shire (Lexington, Massachusetts), TearLab, TearScience, and TopiVert (London). Contact information Pflugfelder: stevenp@bcm.edu Sheppard: jsheppard@vec2020.com Tools continued from page 36

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