Genomics revolutionising opthalmology

One of Britain's leading experts in ophthalmology and genomics has been named in the Queen’s birthday honours list for his services to these disciplines.

Prof. Graeme Black of the Central Manchester University Hospitals NHS Foundation Trust has been honoured with an OBE (Order of the British Empire) - one of the highest civil awards in the UK. We spoke to Prof. Black about the OBE and looked at some of the reasons why he has received such a prestigious award:

“Inherited ophthalmic disorders and particularly inherited retinal dystrophies have served as a paradigm for developing molecular analyses of genetically heterogenous conditions. We have a long and successful record of disease gene identification and mutation detection using a combination of genomic approaches. Consequently our molecular diagnostics services have much higher success rates which represents a remarkable transformation in efficacy over the past three to five years.” Said Prof. Black.

Professor Black’s strategic leadership has been integral to Manchester becoming one of the world’s leading centres for inherited ophthalmic diseases. The team, which he has built, represents one of the brightest and best multidisciplinary clinical services in the UK and has worked extensively to integrate genetic testing, bioinformatics and next generation sequencing (NGS) into general clinical practices.

Prof. Black said: “We hear a lot about translational medicine, a lot about the ability of biomedical science to improve healthcare. I believe that genomic medicine is one of the areas that will be at the forefront of it all. Those technical changes are being translated into medical practice and implemented as we speak. Right now, here in Manchester, we’ve seen diagnostic rates improved from 5% to 75% for ophthalmology.”

Rare diseases affect as many as 3.9 million people in the UK1 alone and, of the eye diseases, 80% of these are genetic in origin1. In fact, it goes deeper: 60% of all cases of blindness amongst children are hereditary and 40% of all ocular misalignments manifest in those with a family history of eye diseases1. Efforts are underway at the moment in Manchester and around the world to identify all the genes in question.

The eye itself is an incredibly complex organ and this is mirrored in its genetic make up, as at least 90% of all of the genes in the human genome are expressed in one or more of the eye’s many tissues.

Prof. Black joined CMFT in 1995 as a Wellcome Trust Clinician-Scientist Fellow. His recent royal reward is a recognition of his foresight in the care potential that genomics can unlock. The disease prevention, prediction and treatment possibilities that have come with it led to him overhauling the infrastructure, investment and research at CMFT in order to improve the diagnosis, management and treatment of inherited genetic visual disorders.

During his 22 years at the Trust, Prof. Black has championed the use of genomic information in clinical care, and he has been able to redefine the delivery of personalised care for patients with a variety of inherited eye disorders throughout the UK.

Prof. Black believes that improvements in diagnosis will drive improvements in treatment and that these changes will be felt by all patients. An accurate diagnosis underpins everything done and attempted in medicine. The difference that genomics makes is that, particularly with cancers, heart disease or conditions like hypercholesterolemia, those early diagnoses save lives.

“The rate of change has been high and there’s no question that it's accelerating in pace with the amount of sequencing we generate.” Prof. Black went on, “our ability to deploy this data and use it to fight serious diseases is getting better and better. Genomic knowledge is expanding and personalised medicine is becoming a reality for oncology, pediatrics and adult medicine. I have no doubt that this is the future of medicine.”

Though NGS isn’t cheap, it is more cost effective than the raft of invasive tests, retests and clinical decision meetings that can take place over a lengthy diagnostic odyssey, and that is not taking into account the stress generated for the patients and their loved ones. This is one of the biggest strengths of genomics in such fields, the ability to eliminate much of that diagnostic odyssey, especially in rare diseases where it can commonly take months if not years to be accurately diagnosed and treated. For example, the average diagnostic odyssey for a UK patient is 7.3 clinicians and 4.8 years to reach diagnosis but with new genome sequencing & analysis technologies it can be as little as 1 clinician and just 5 days.

These methods aren’t without their own complications. Some of which are as simple as the growing need for expertise amongst clinicians, doctors and consultants to keep pace with the technology and developing methods. Some are in security, such as the need for privacy and consent due to potentially damaging unexpected findings presented in the results and the implications of hereditary disease on the other family members - all of which are further heightened by the deeper legal complexities surrounding children.

At the core of Prof. Black’s work in genomics have been ground-breaking advances in both sequencing technologies and in clinical genetics analytics platforms, which have enabled the labs to go from offering testing in around 10% of cases to testing almost universally. This wasn’t possible before, as the cost and time requirements were simply too high to be practical, but technological breakthroughs have empowered clinicians to get results much faster and more accurately. The shift in aetiology due to this has been enormous.

“As fast as the technology moves,” Prof. Black added, “we must be mindful that broadening access to genetic testing and counselling will be crucial to realizing the benefits of personalized healthcare and must be supported by a clear understanding of the necessity in standardizing genomic care.”

Software and associated databases also enable clinicians to provide lists of potentially disease-causing variants that can be assigned pathogenicity by users and can be added to at any time creating a living and ever-growing frame of reference from which clinicians and doctors can save even more lives in the future.