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EW INTERNATIONAL 64 May 2015 by Matt Young and Gloria D. Gamat EyeWorld Contributing Writers "But currently there is no therapeutic treatment apart from tissue replacement in the form of a transplant procedure," Dr. Mehta said. "The problem is, since this is a protein aggregation disease over time, as the protein accumulates, the disease continues to get worse." Further explaining the value of genetic testing in corneal stro- mal dystrophies, Dr. Mehta noted that the speed by which the disease will get worse is dependent on the mutation. In addition, knowledge about the specific mutation has been shown to influence the disease r - currence if the patient is to undergo transplantation in order to improve visual acuity. "Knowledge of the mutation will tell the likelihood of needing a transplant in the first place," he said. "Hence, if we know that there is a high risk of recurrence [from the mutation], we will only offer deep anterior lamellar keratoplas- ty [DALK] instead of penetrating keratoplasty [PK]. The reason being is that if we have to change the cor- neal transplant following recurrence, second time graft survival following DALK is better than PK." Available in Singapore since September 2014, the POLARIS TGFBI test has changed the course for clini- cians in terms of managing corneal stromal dystrophies. For patients who have clini- cal manifestations of the disease, genetic testing will provide informa- tion about the long-term prognosis, effort involving many doctors and scientists from different medical and research institutions in Singapore. "It took approximately 18 months to set up the genetic test and to get all the validations done," he said. Performing genetic testing in patients with or without clinical manifestations of TGFBI symptoms has numerous advantages. Since there are considerable interfamilial and intrafamilial phenotypic varia- tions, genetic testing will help con- firm the diagnosis. Also, phenotypic presentation varies greatly among different ethnic groups. Therefore, genetic testing will confirm the dia - nosis irrespective of racial group. "Most importantly, genet- ic testing provides information about prognosis in an individual patient, counseling for families of the affected patient, risk assessment for patients who are undergoing transplantation with respect to disease recurrence, and can provide a prediction risk for family members of patients who are affected if they are to undergo eye surgery such as LASIK," Dr. Mehta said. How genetic testing is changing the game Traditionally in the management of corneal stromal dystrophies, most clinicians had to rely on clinical diagnosis alone, which had severe limitations. The standard course of treatment has been to treat any symptomatic problems such as re- current erosion syndrome. Asia's first genetic test for corneal stromal dystrophies is made in Singapore V ia collaborative medical research in Singapore, a team of eye doctors and scientists has developed the POLARIS TGFBI (transforming growth factor, beta- induced, licensed to Asia Genomics, Singapore) test, Asia's first genetic test for corneal stromal dystrophies. As a group of genetic disorders affecting the cornea that can lead to blurring and vision loss, corneal stromal dystrophies are known to be caused by progressive accumulation of deposits within the stroma— deposits that were not caused by inflammation, infection, or trauma, but by genetic mutations that lead to abnormal proteins. These abnormal proteins result in the accumulation of insoluble material within the stroma. The one gene responsible: TGFBI gene "There are many inheritable con- ditions that affect the cornea," said Jodhbir Singh Mehta, MD, senior consultant and head of research, cor- nea department, Singapore National Eye Centre (SNEC), and director for clinical translational research, Singa- pore Eye Research Institute (SERI). Dr. Mehta emphasized that out of all the inherited corneal dystro- phies, TGFBI corneal dystrophies are the most well-characterized. In 2007, Francis Munier, MD, head of the retinoblastoma and oculogenetic unit, Jules Gonin Eye Hospital, Lausanne, Switzerland, and colleagues, discovered that muta- tions in the TGFBI gene caused cor- neal stromal dystrophies. Since then, there have been reports of more than 60 mutations in the literature. Previously, all the phenotypic manifestations were thought to be caused by different genes, resulting in a dilemma for clinicians. "The discovery that one gene was respon- sible for many phenotypic changes in the cornea was a major discov- ery," Dr. Mehta said. The POLARIS TGFBI test was subsequently developed, according to Dr. Mehta, by a collaborative Genetic test for corneal stromal dystrophies now available G enetic testing offers clinicians a powerful tool to help inform and counsel patients. The latest addition of a new test for corneal stromal dystrophies is a welcome addition. The groundbreaking work on this was done in Singapore. Once it was understood that a single gene was associated with a variety of phenotypic presentations, it become prac- tical to develop genetic testing to identify patients at risk. There is no doubt that this will help guide clinical decision making as well as help affected patients and family members understand their condition and plan for the future. John A. Vukich, MD, international editor Dr. Mehta is the lead scientist who developed the genetic test POLARIS TGFBI. Source: Singapore National Eye Centre International outlook