EyeWorld Asia-Pacific September 2015 Issue

62 EWAP NEWS & OPINION September 2015 to the potential riches hidden within all that waste. Imagine, for instance, all the tears collected during a simple Schirmer’s test, disclosing no more information to the diagnostician than volume or rate of production. Moreover, imagine all the epithelial tissue excised, aqueous and vitreous humor aspirated, simply discarded during numerous types of surgery. The number of cataracts removed following cataract surgery, the amount of crystalline lens material extracted during lens exchange, particularly in high-volume ophthalmic surgery practices. Have you ever wondered: What are we missing by discarding all this material? One ophthalmologist has. His idea, presented at the final cataract surgery symposium on the last day of the 28th APACRS annual meeting, is being hailed as revolutionary and even Nobel-prize worthy. Rohit Shetty, MD , Bangalore, India, had a simple request concerning all this waste: “Don’t discard! Send it to the lab.” “The future of medicine is not an extension of your past,” he said. “Just because we are very comfortable with what we have today, and we have the answers to a lot of stuff, just does not mean that we have to stick to it.” In fact, rather than proceeding necessarily from past experience, the philosophy behind Dr. Shetty’s approach seems focused almost exclusively in the moment, proceeding from case to case, treating every individual as unique, the idea being to create a more “bespoke” approach to medicine. Consider how drugs are developed and tested for, say, dry eye. Numerous agents have been developed to act on certain inflammatory biomarkers associated with the condition. But, asked Dr. Shetty, how sure are we that a particular patient’s particular form of the condition is influenced by these markers? This, he said, is why not all patients respond to the same drugs. The center of attraction for this approach? “Everything you discard.” In the above case, tears collected during a Schirmer’s test used in the diagnosis of the dry eye condition could be analyzed for TNF-a, MMP9, LOX, NF-k8, vitamin D and other biomarkers which can aid in the assessment of conditions as diverse as keratoconus, uveitis, glaucoma, retinopathy of prematurity (ROP), orbital inflammatory disease, and even degenerative markers in neurological diseases such as Alzheimer’s—in addition to dry eye disease. This analysis could be used to develop a more targeted— bespoke—therapeutic regimen. Dr. Shetty identified other biomarkers now known to be found in certain tissues: corneal epithelial tissue can be analyzed for WNT-3, SOX 17, IL6, TGF-B, TIMP I, Col IA which are found on the corneal haze pathway and wound healing; corneal lenticules can be tested for TGF-B, Col IA, IL 6, Col IVA, and vimentin which can be used in keratocyte cultures and drug testing, and to assess tissue inflammatory response; aqueous humor can be tested for CD 4 cells, VEGF, and viral markers to assess graft rejection, uveitis, pseudoexfoliation, diabetic retinopathy, and congenital cataracts; lens matter can be tested for a-SMA, PITX-3, and HSPA-4 to elucidate the etiopathogenesis of cataract formation; vitreous can be tested for VEGF, miRNA, and TGF-B for VEGF assays, to test genetic predisposition to VEGF response, and as indicators in the management of diabetic retinopathy. Dr. Shetty believes that a “titrated approach,” customizing therapies based on what are actually contained in a patient’s discarded tissue, the vast repositories of information contained within all that so-called waste, is the future. All the laboratory tests involved—putting tissue through genetic analysis, quantitative RT-PCR, DNA synthesis, immunohistochemistry, mRNA extraction, flow cytometry, immunofluorescent studies, and more—may seem complicated and daunting, but Dr. Shetty reassured the audience this would not remain so in the future: Dr. Shetty believes at least some of these tests will eventually come on a chip. “I’m sure this will become much simpler over time, and will become the normal routine in our practice.” “Please do not hesitate to send all these things to the lab,” he added. “It will help us in some way or another to understand.” Live reports - from page 61