Dry eye biomarkers

Tear-based biomarkers are bringing a new era in the diagnosis and treatment of diseases of the ocular surface and cornea, according to Rohit Shetty MD, PhD, FRCS, of Narayana Nethralaya Eye Hospital, Bangalore, India. “A Schirmer’s test strip, which we generally discard, can be used to diagnose, prognosticate and even help in developing drugs to treat dry eye and other diseases. That is why we say: ‘Please do not discard what could probably be a gold mine that could give us a completely new understanding of the disease’,” Dr Shetty told the 21st ESCRS Winter Meeting in Maastricht, The Netherlands. He noted that he and his associates are developing a database of their patients tear film components in their laboratory. Using molecular profiling techniques and artificial intelligence technology, they are building biomarker profile and integrating it with clinical status and outcome of the diseases under investigation. He also stated that his team and others have identified tear-derived biomarkers for dry eye, keratoconus, as well as systemic diseases including autoimmune disorders, Alzheimer’s disease, and breast and prostate cancer. Dr Shetty added that he and his associates are in the process of developing a tear sampling device prototype to enable point-of-care testing for biomarker levels in clinics, rather than in the laboratory. “Over the next decade, tear fluid testing will become as important as blood and urine testing,” he predicted. An in-depth understanding of the eye’s immune status and function is necessary to appreciate the clinical relevance of these biomarkers for dry eye, Dr Shetty said. Inflammation is a key factor in the evolution of dry eye. The tear-derived inflammatory biomarkers for dry eye include TNF-alpha, interleukin 6 (IL-6), IL-8 and IL-17, which are all elevated in eyes with the condition. Once set in motion by tear film instability, inflammation leads to changes in neuronal behaviour, an increase in corneal sensitivity, and reduces goblet cell density and mucin secretion, disrupts the corneal barrier function and impairs epithelial healing. Hence, blocking inflammation can prevent these sequelae, Dr Shetty said. Tear-derived biomarkers can also help explain some of the complaints of patients with ocular surface discomfort, in whom none of the clinical signs are apparent, he added. As an example, he presented a case of a patient with ocular pain following LASIK that could not be explained with the usual testing techniques. Tear-based biomarker testing revealed abnormally high levels of nociceptive factors as well as low levels of anti-nociceptive factors. Another finding of the Bangalore team was that haze following photorefractive keratectomy (PRK) correlated with increased gene expression of IL-6 and chemokine CXCL10, and decreased expression of WNTA and SOX17. They have also completed a tear biomarker based study suggesting that eyes that have undergone small incision lenticule extraction (SMILE) surgery have a more favourable corneal healing response than eyes that have undergone LASIK. Dr Shetty and his associates compared the postoperative tear-derived biomarker profile of eyes in a series of patients undergoing either LASIK or SMILE. They found that those undergoing LASIK had increased levels of molecular factors that are associated with inflammation and corneal tissue remodelling. In contrast, those who underwent SMILE had relatively lower levels of those molecular factors in their tears. Tear-derived biomarkers can also provide an indication of the likelihood and extent of disease progression in eyes with keratoconus. For example, Dr Shetty and his associates have demonstrated that tears from eyes with keratoconus had high levels of interleukin-6 (IL-6) and matrix metalloproteinase 9 (MMP9), and the levels corresponded with the severity of disease. They have also shown that the treatment of keratoconus patients with topical eye drops containing cyclosporine A reduced both tear MMP9 levels and progressive steeping of the affected corneas. Rohit Shetty: drrohitshetty@yahoo.com

Tags: cornea, dry eye