Retina 2016 was officially opened by Mary Mitchell O’Connor TD, Minister for Jobs, Enterprise and Innovation, who generously shared that the work of Fighting Blindness is “very personal” to her as she “has seen up close the challenges, difficulties and stresses faced” by people who have lost their sight. She noted that “many conferences are all about the experts, but Retina 2016 goes much further” and thanked Fighting Blindness for their consideration in including all stakeholders in this event.
Loretto Callaghan, Managing Director, Novartis Ireland emphasised the importance of partnering with the public and patients. Novartis Ireland also supported Fighting Blindness in their call to government to publish and implement the National Eye Care Plan, which is currently under development.
Kevin Whelan, CEO of Fighting Blindness stressed that while researchers are working hard to secure the cure, it is “incumbent on Fighting Blindness to do justice to the people we represent by ensuring we are well positioned to ensure they have access to treatments and cures as they arise.”
The Scientific Programme began with a clinical research presentation from Prof Andrew Lotery, University of Southampton who from his experience in the clinic, provided examples of cases of a frequently undiagnosed condition called Sorsbys Fundus Dystrophy. This is an early onset form of macular degeneration involving both a peripheral retinal dystrophy that can cause night blindness and a central retinal disease, similar to what is observed in age related macular degeneration (AMD). Prof Lotery cautioned that this condition may be more common than we think. He highlighted the necessity to genetically test people in whom a diagnosis isn’t clear and in individuals who present with early onset AMD. Prof Lotery also described his experience of treating the neovascular or wet form of the disease using anti-VEGF injections and indicated many new approaches and innovations that may lead to future treatments of the disease.
Genes and gene therapy was the topic of discussion for the rest of the morning and we were delighted to welcome back to Ireland, researcher Dr Michael Redmond, National Eye Institute (NEI), United States. Dr Redmond received his PhD from University College Dublin before moving to the US where he and his team discovered a protein called RPE65 that is essential for normal vision. The way in which this protein functions has been the focus of his research for a number of years and in his presentation, Dr Redmond described how his lab use mouse models to determine the role of RPE65 in vision, particularly the minimum amount of this protein required for photoreceptors to function.
Continuing the discussion on the role of RPE65, we heard from Spark Therapeutics, a US based company which has developed a gene therapy for a rare form of blindness known as Leber congenital amaurosis (LCA). Specifically, their therapy is for a particular form of LCA known as LCA2 that is caused by mutations in the RPE65 gene. Dr Daniel Chung, Ophthalmic Lead for Clinical Development at Spark Therapeutics discussed the development and design of a primary endpoint for a Phase 3 trial for inherited retinal degenerations. This endpoint is the test by which it is determined whether the treatment being tested has been beneficial or not. Spark Therapeutics were tasked with identifying a functional endpoint and developing a way in which they could capture and show that functional vision had improved following treatment. To achieve this, participants in the study were assessed on their ability to navigate an obstacle course or maze under various light levels.
Results from the study presented by Dr Chung demonstrated that following treatment, participants significantly improved their ability to navigate the course under very low light conditions indicating an improvement in their vision. Spark are currently in the process of applying for market approval for this product from the Food and Drug Administration (FDA) in the US.
We also heard from Prof Frans Cremers, Radbound University Nijmengen Medical Centre, Netherlands who illustrated the complexity in identifying causative gene mutations for inherited retinal conditions. To date, more than 250 genes are known to be associated with inherited vision loss but yet a likely disease-causing gene has only been established for approximately 60% of patients. Therefore, for 40% of people living with an inherited retinal degeneration, a causative gene mutation cannot be currently identified. Prof Cremers emphasised the necessity to look more closely at the known genes for the unknown 40%, as many of the unidentified mutations may reside in the non-coding regions that represent 98% of the human genome.
Fighting Blindness funded researcher, Prof Jane Farrar, Trinity College Dublin described how we are now in a new era of gene discovery and diagnosis. She gave an overview of her role in characterising forms of retinal degeneration in the Irish population. She explained that genetic diagnosis is facilitating, when appropriate and with consent, moving people towards clinical trial. Prof Farrar also introduced work her group has been performing towards the development of gene therapy for a number of inherited retinal degenerative conditions. You may recall from articles earlier this year that the spin-out company Genable which was developing one of these gene therapies, for rhodopsin linked autosomal dominant retinitis pigmentosa (RP), was acquired by Spark Therapeutics to take it to the next stage of development.
Following on from previous discussions, Prof Elfride De Baere, University of Ghent, Belgium reiterated the theory that many of the unknown genetic variations in inherited retinal degenerations may be located in the non-coding regions of the genome.
At Fighting Blindness, we believe the Retina Conference is a unique and fantastic platform for young researchers and clinicians to engage and interact with pioneering experts in the field of retinal research. This year, three young researchers and clinicians were invited to give short oral presentations. Conor Daly (University College Dublin), Dr Louise Porter (University of Liverpool, UK) and Andrew Smith (University College Dublin, currently placed at the National Eye Institute in the US) presented their work to the international audience.
The afternoon research presentations began with an insightful discussion on the applications and potential of cell therapy as a treatment for retinal degenerations. There are currently two major strategies for stem cell therapies – ‘preservation’ and ‘replacement’. To date, much of the focus has been on retinal pigment epithelium (RPE) cells because these ware generated more easily and also more readily transplanted. Photoreceptor transplantation is a more difficult task because of the requirement for functional connectivity with nearby cells.
We were honoured to host Dr David Gamm, University of Wisconsin who told attendees about his work growing light-detecting cells using stem cells. His talk highlighted the current state of this stem cell technology and its anticipated applications to the treatment of inherited retinal degenerative diseases. He described how in a petri dish, his group has used this technology to grow human cells in a 3D environment that mimics the human retina. He emphasised that there are many things researchers can study and determine in a dish and still have great impact and relevance to patients. For example, these models can be used to better understand the disease, test potential treatments such as gene therapy, gene editing or investigate drugs that may slow down a particular process. Dr Gamm very kindly gave his time to speak to a number of journalists during the conference. We are very grateful to him for helping raise awareness about Fighting Blindness and vision research in this way.
It was a pleasure to welcome Prof Robin Ali, University College London, Chair of Fighting Blindness Medical and Scientific Advisory Board. Prof Ali gave an impressive overview of how his group has approached the task of trying to develop a photoreceptor cell replacement therapy for retinal degeneration. Prof Ali provided an update on their latest and exciting work on differentiating and transplanting embryonic stem cell derived cone photoreceptors in animal models.
We also heard from Dr Shaomei Wang, Cedars-Sinai, Los Angeles who described the use of induced pluripotent neural stem cells as a strategy to preserve the remaining photoreceptors and protect the existing retinal anatomy and function. Dr Wang believes that stem cell therapy may offer a real hope to individuals affected by age-related macular degeneration (AMD).
Moving away from the topic of cell therapy, Prof Bart Leroy, University of Ghent, Belgium presented an engaging clinical research perspective on his experience in the clinic. Prof Leroy described the genotypes and phenotypes in people who have bestrophinopathies, primarily caused by mutations in the BEST1 gene, and indicated how gene therapy could work for these conditions.
Prof Austin Roorda, University of California described the fascinating work that he does to study structure and function in the eye using adaptive optics. Adaptive Optics is a technology that gives a sharp image of the living retina and allows us to see what is happening on a single cell basis. Its use is a crucial element in the fight to prevent, slow and cure eye disease in the retina. Thank you to Prof Roorda for giving his time to speak on Irish radio while here for the conference.
It is crucially important that Retina also features presentations from individuals who are living with vision loss. Peter Ryan, Paralympic cyclist described eloquently his experience of losing his sight and the difficulty in learning to accept this. He reminded us all that while eyesight is far from a simple subject, day-to-day vision is a beautiful thing and the simplicity it gives a life cannot be measured in words. John Delany, Senior Counselling Manager at Fighting Blindness expressed his admiration at the commitment, enthusiasm, optimism and determination of people to find answers to very difficult questions. John spoke on the importance of relationships and encouraged all clinicians, researchers and patients sitting in the audience to set about building connections and relationships that will make a difference in their quest to find cures and treatments for blindness.
The conference was closed by Christina Fasser, President of Retina International. Following presentations from scientists, clinicians and patient testimonies, Christina reminded us that we are all working and hoping for the same thing which are treatments coming from the lab bench, going to clinical trial and ending up with patients.
Thank you to everyone who submitted an abstract to Retina 2016. Andrew Smith, University College Dublin was awarded the Geraldine Duggan Award for his presentation. Geraldine Duggan was one of the founding members of Fighting Blindness and her daughter, Suzanne Duggan, presented the award in her memory. Dr Sarah Roche, University College Cork was awarded the prize for ‘Best Poster’.