Genomics in cornea care

Dr Davide Borroni MD, from the Fondazione Banca degli Occhi del Veneto, Italy, has won the 2018 ESCRS Clinical Research Awards. Dr Borroni’s research project will look at the potential for genomics technology to more rapidly and accurately identify corneal infectious agents in order to guide clinical management. The ESCRS Clinical Research Awards, now in its seventh year, provides research funding of up to €750,000 over a three-year period and is open to all ESCRS members (with at least three years’ ESCRS membership) and a full-time clinical/research post at an EU-based clinical or academic centre. The Awards are designed to support, encourage and fund individuals that actively conduct clinical research in the field of cataract and refractive surgery, and to facilitate and support an independent culture of clinical study for the ultimate benefit of improving patient care and outcomes. Dr Borroni, a graduate of Insubria University, Varese, Italy, undertook specialist ophthalmic training in Rīga Stradiņš University, Latvia, where, working with Prof Guna Laganovska, he developed an interest in the practical use of genomic technology in clinical care. His surgical interests include cataract, refractive surgery and corneal transplantation, while his clinical interests include translational medicine, corneal diseases and infections. In 2016 Dr Borroni completed a training in medical and surgical cornea, the year after joined The Venice Eye Bank Foundation and The Royal Liverpool University Hospital to develop new diagnostic methods for corneal infections. Currently he is undertaking a surgical fellowship in cornea, refractive surgery and advanced ocular surface disease at The Royal Liverpool University Hospital in the St Paul’s Eye Unit. The novel research to be funded by the ESCRS will be focused on the use of whole genome sequencing technology to study ocular surface microbial communities directly in their natural environment. Dr Borroni told EuroTimes: “Ocular infections are an important cause of ocular morbidity and worldwide blindness. Diagnosis of these infections is challenging due to low specificity and sensitivity of currently available assays, inability to collect suitable clinical samples and difficulty for many clinicians to recognise and treat ocular infections appropriately. Rapid advances in sequencing technology and bioinformatics have made metagenomics a fertile area for developing clinical diagnostics and therefore prompted us to evaluate a hypothesis-free approach to identify ocular infections by performing unbiased metagenomic deep sequencing on clinical samples.” Metagenomics refers to a field of research that is fast becoming a central tool for identifying a broad range of organisms through their unique genetic sequence. In broad terms, the approach refers to the use of high-throughput DNA sequencing to provide taxonomic and functional profiles of microbial communities without the need to culture the microbes in the lab. Dr Borroni explained that “less than 2% of bacteria can be cultured in the laboratory and therefore metagenomics tries to overcome this by developing and using culture-independent approaches to identify the 98% of microbes that resist culture techniques – whether they are prokaryotes, eukaryotes or viruses”. A fundamental aspect of the proposed research aims to use the hypothesis-free approach facilitated by metagenomics to directly identify infectious agents and then use such information to guide clinical management. At present, patients with corneal infections are treated with a broad spectrum of antimicrobial agents while laboratory culture techniques attempt to grow and identify the bacterial or fungal agent causing the infection. Oftentimes such techniques may either fail to detect an agent or simply take too long to provide a clinically useful result. Instead of trying to culture the infectious agent or use defined polymerase chain reaction (PCR) primers to fish out known pathogens, Dr Borroni’s approach will follow a “shotgun” strategy whereby a corneal scrape will be taken, to which the metagenomics approach will aim to sequence everything that is in the patient’s sample. The genetic information obtained will be cleaned of human DNA sequence and then compared with the genetic microbial profile of a normal eye. The result should provide a quantitative picture of gene signatures detectable in the infected eye, allowing the clinician to identify the likely causative agent and then determine the optimal medical management. Dr Borroni’s research project, entitled “METAgenomics guided treatment of CORneal infections – a blinded interventional randomized clinical trial” (META-COR), will recruit an estimated 160 patients and will involve a team of up to 15 ophthalmologists across several EU locations including sites in Latvia, Italy, United Kingdom, Sweden, Greece, Austria and Spain and the University of Maryland in US. The main clinical centre will be at the Royal Liverpool University Hospital under the supervision of Prof Stephen Kaye and Mr Vito Romano, and the laboratory for the Metagenomics study will be the Centre for Integrative Biology (CIBIO) at University of Trento (Italy) under the supervision of Prof Nicola Segata. EuroTimes will aim to update readers on the progress of this exciting study as results become available. Davide Borroni: Davide.Borroni@fbov.it

Tags: ESCRS Clinical Research Awards