Retina 2014 was our biggest and most successful conference to date with three days of activity running from Thursday, November 6 to Saturday, November 8. The conference once again brought together our leading vision researchers and eye doctors from across Ireland, along with invited international speakers and guests. One of the highlights was our Saturday public engagement meeting, where our members had the opportunity to hear about advances in retina research direct from the individuals involved.
Thursday, November 6: Clinical Trials Meeting
Following a successful initial meeting last year, we once again held a small clinical trials meeting at ICON Clinical Research in Leopardstown, Dublin. The purpose of this workshop was to discuss some of the roadblocks that face the development of clinical trials and that will influence the ultimate success rate of these trials, with a focus on diseases of the retina. We were delighted to have a number of our Irish scientists and clinicians in attendance along with our international speakers. Representatives from the broader clinical trials environment also gave their input into the meeting including attendees from the Irish medicines regulator the HPRA and also from the government organisation Enterprise Ireland, who are responsible for developing innovation and investing in Irish enterprise. As a patient-led organisation, it was important to have the patient voice centrally involved in the discussion, and a number of patient representatives gave strong testimonies during the meeting regarding their personal, lived experiences with vision impairment and their expectations regarding efficacy of new therapies. We would like to sincerely thank Prof Brendan Buckley, Chief Medical Officer at ICON Plc and Fighting Blindness Medical and Scientific Advisory Board members for facilitating and supporting this meeting.
Friday, November 7: Scientific Programme
The Scientific Programme of Retina 2014 took place in Croke Park from 8am to 5pm and was very well attended with over 120 researchers, clinicians and students.
We began the day with a breakfast meeting entitled ‘Translating Basic Vision Research’. We were delighted to have Siobhan Gaynor, the Operations Manager at Genable Technologies Ltd and Dr Ruth McMahon, Commercialisation Specialist at Enterprise Ireland, speak in this session about the important steps that scientists involved in research need to be aware of early in their careers in order to translate their laboratory findings to a treatment application. This was a very informative session which generated a lot of discussion amongst the audience and really set the tone for the rest of the day.
Fighting Blindness CEO, Avril Daly and Consultant Ophthalmic Surgeon and Fighting Blindness Board Member Mr David Keegan then welcomed everyone to Retina 2014 before introducing Minister for Health, Mr Leo Varadkar, T.D. to officially open the conference. Speaking during his opening address, Minister Varadkar said, “This is an exciting time for the vision health community, especially patients and families who are affected by sight loss. The innovative and pioneering work presented today is incredibly important and gives hope to the 224,000 people affected by sight loss in Ireland, and to future generations affected by genetic eye disease. It’s really encouraging to hear about the huge progress being made in treating blindness, thanks to the dedication of those working in research and vision health, and the commitment of organisations like Fighting Blindness.”
Following the Minister’s address, some of the world’s leading vision researchers presented their work. An overview of each presentation is outlined below.
Prof Gustavo Aguirre
Professor of Medical Genetics and Ophthalmology, University of Pennsylvania School of Veterinary Medicine, USA
Prof Aguirre is an esteemed veterinarian researcher whose seminal work in identifying, then treating dogs with a form of Leber congenital amaurosis was a critical step in moving gene-based treatments into human clinical trials for retinal disease. Gus updated the conference on his latest research where his lab has identified a number of other retinal diseases in dogs, which act as a model for learning more about the human equivalent conditions. These include dog models of Best disease, achromatopsia, and a form of X-linked retinitis pigmentosa caused by mutations in the RPGR gene. Proving the efficacy of gene based treatments in dogs provides a key pathway for translation of this work towards therapy development in humans.
Prof Robert MacLaren
Professor of Ophthalmology at the University of Oxford, Consultant Ophthalmologist at Oxford Eye Hospital, UK
Prof MacLaren gave an update on the impressive initial results from his phase 1 clinical trial for choroideremia. In this trial, published earlier this year, six men with the condition were injected with a viral construct containing the REP1 gene. Robert explained the surgery involved in this technique. Firstly, a controlled surgical retinal detachment is preformed involving the creation of a “bleb” and the gene therapy is then delivered to make direct contact with the photoreceptor cells of the retina. Two patients in this trial had quite advanced choroideremia and thinning of their retinas. Detachment of the retina normally leads to reduced vision; however these patients both had significant gains in vision. The team suggests that this justifies the use of this approach and lends support for further assessment of gene therapy for choroideremia.
Dr Giuliana Silvestri
Consultant Ophthalmic Surgeon and Reader, Royal Victoria Hospital and Queen’s University Belfast
Dr Silvestri has been a longstanding leader and champion of research into conditions affecting the retina over the past number of years in Northern Ireland. In her presentation Julie outlined the history of work in Northern Ireland where the early need was recognised for a comprehensive database for retinitis pigmentosa, by Mr Brian Page in 1988. This work was subsequently expanded by Julie’s own team in order to provide clinical diagnoses and access to genetic counselling services. Julie gave a number of examples where the knowledge provided by molecular diagnosis has impacted directly on patient management, showing the power of such an approach. We are delighted that Julie will continue to input her expertise and experience by the recent integration of her work within the all-Ireland project known as Target 5000, which is spearheaded by Fighting Blindness.
Dr Matthew Campbell
Research Assistant Professor in Genetics, Department of Genetics, Trinity College, Dublin
Dr Campbell kindly acknowledged the PhD research scholarship he received from Fighting Blindness back in 2002 which lay the foundation for the many accolades he has received on his way to establishing his own research programme last year. The subject of Matthew’s presentation was that of the inflammasome. He introduced these protein complexes that are often referred to as the ‘defence guardians’ of the body. Matthew and his team have researched the complex manner in which the inflammasome can regulate progression from the dry form to the wet, more advanced form of age-related macular degeneration (wet AMD). His team have discovered that one particular inflammasome, known as NLRP3, can regulate the production of a molecule known as IL-18, which when administered to mice has been shown to work more effectively, in combination with current treatment injections, at stopping the development of the wet form of this prevalent condition. His team have teamed up with a large pharmaceutical company to work on proving intravritreal (injection into the eye) safety of this compound before progression to a future human clinical trial.
Prof Marius Ader
Cell Replacement in the Mammalian Retina Research Group Leader (CRTD), Dresden, Germany
Prof Ader was delighted to speak in Dublin, where he had spent a number of happy years as a postdoctoral research fellow in Prof Jane Farrar’s laboratory in Trinity College, Dublin, before his return to Germany in 2007. Many promising gene therapies focus on maintaining visual function; however there are currently no established therapies available to replace visual function once it is lost. Marius’s research concentrates on cell replacement strategies to replace the critical photoreceptor cells in mouse models of retinal degeneration. Unlike other studies in this area, his team focus on transplantation of the cone photoreceptor cells that function in daylight conditions, unlike the rod cells which we mostly rely on for our evening and night vision. Marius explained that advances in the field have overcome previous concerns over the generation of sufficient numbers of transplantable cells, and the focus has shifted towards increasing the amount of transplanted cells that become functionally integrated into the degenerated retina. Promising results from these studies provide the first proof-of-concept for the feasibility for the restoration of daylight vision after transplantation in the mammalian retina.
Mr Tim Jackson
Consultant Ophthalmic Surgeon, King’s College Hospital and Senior Clinical Lecturer, King’s College London, UK
Mr Jackson’s presentation focused on his surgical and scientific experience in the area of bionic vision, also known as artificial vision. Tim gave an overview of the main approaches in this field, which vary in where the chip is placed in the retina; some are placed under the macula (sub-retinal) and some are placed on it (epi-retinal). He also explained that this placement affects external prosthesis – the epi-retinal devices require external glasses, in contrast to the sub-retinal which does not. Tim acknowledged that huge advances in this field have been made and will continue apace, however the vision regained at the moment is quite rudimentary, and functions primarily as an aid to mobility rather than a replacement of vision. Tim finished his presentation by thanking the many patients who, after being informed about the lengthy and invasive surgery for the sub-retinal device, took part in his clinical trial site; further increasing the scientific and clinical knowledge in the area of artificial vision.
Dr Mark Pennesi
Assistant Professor in Genetics, Casey Eye Institute, Oregon Health and Science University, USA
As someone who has a clear understanding of both the clinical and scientific aspects of retina research, Dr Pennesi gave an inspiring presentation detailing some of the many gene therapy clinical trials that he is working on for inherited retinal conditions, under the direction of Dr Richard Weleber in the Casey Eye Institute in Oregon. Gene therapy for a form of Leber congenital amaurosis, LCA2, recruited children as young as six years old in a recently-closed clinical trial, pointing to the safety of the approach in this group. His team are currently involved in a Stargardt disease and an Usher syndrome Type 1B gene therapy clinical trial where ABCR and MYO7A genes respectively are delivered via lentiviral constructs. Twenty patients have now been treated between these two trials and no adverse consequences have yet been reported, with results to follow. Expansion is to follow with clinical trials for conditions such as X-linked retinoschisis and achromatopsia currently being planned. Mark however, cautioned enthusiasm by emphasising the urgent need for investment in natural history studies of conditions affecting the retina. These natural history studies provide information on the natural course of a disease allowing researchers to design ‘smarter’ clinical trials and aid in the approval of new therapies.
Prof Donald Zack
Professor of Genetic Engineering and Molecular Ophthalmology at the Wilmer Eye Institute, Johns Hopkins University, USA
Prof Zack opened his presentation by acknowledging the huge strides that have been made in identifying the more than 200 genes that, when mutated, can cause retinal degeneration, leading to the exciting advances in gene therapy that had been described earlier in the day. However, the limits to this approach are clear as not every gene mutation will be amenable to gene therapy and such therapies may not be viable as they may only be appropriate for a small fraction of patients. Don and his team take a different approach, they are interested in developing neuroprotective therapies that are suitable for many different genetic subtypes of the one condition, for example subtypes of retinitis pigmentosa. In his presentation, he described a technology known as high-content screening in order to discern between thousands of drug compounds for their role in promoting the survival of photoreceptor cells, with the hope of identifying molecules that can be taken to the next step as leads for clinical drug development. Don also outlined new advances in modelling retinal diseases using induced pluripotent stem (iPS) cells. This relatively new and promising approach involves generating retinal cells from people affected by retinal conditions and can lead to greater understanding by studying retinal degeneration mechanisms. This system could offer a reliable and more-high throughput model for the further testing of promising drug candidates for their effectiveness at slowing down retinal degenerations.
The scientific programme of Retina 2014 was closed by Ms Christina Fasser, President of Retina International. Christina has been a leading voice in the effort to focus attention on the need for scientific research to find a cure or treatment for retinal blindness for over 25 years. She spoke about the importance of patients’ involvement in driving and leading clinical research and advocating for access to therapies when they become available.
Saturday, November 8: Public Engagement Day
Over 200 people attended the Public Engagement Day of Retina 2014 in Croke Park. This was the biggest turnout yet for the annual event and we were delighted to welcome back our long-time members and supporters as well as meet so many patients and families who are new to the organisation.
This was the fourth successive year of the Public Engagement Day, which gives people the opportunity to meet scientists and doctors and hear about new developments, details of clinical trials, discuss topical issues relating to services and healthcare, as well as meeting other patients living with similar conditions.
Fighting Blindness CEO, Avril Daly opened the day’s activities at 10:30am. Avril welcomed everyone to the event and introduced the Fighting Blindness staff who each gave a brief description of their role in the organisation.
Prof Gustavo Aguirre from the University of Pennsylvania in the USA then gave a fascinating overview of the history of gene therapy with his talk ‘The Story of Gene Therapy – Where Are We Now?’
An expert panel discussion about our Target 5000 research project was chaired by Fighting Blindness Research Manager Dr Maria Meehan. The panel included Dr Paul Kenna, Royal Victoria Eye and Ear Hospital, Dublin, Mr David Keegan, Mater Hospital, Dublin, Miss Giuliana Silvestri, Royal Victoria Hospital, Belfast and Dr Matthew Carrigan, Trinity College, Dublin.
This covered the importance of genetic sequencing in terms of diagnostic accuracy and opportunities to participate in potential trials as they arise. It also dealt with the important relationships between patients, doctors and scientists, under the oversight of Fighting Blindness, to establish a patient registry. It was a chance for specific questions to be asked and answered especially in terms of timelines and future possibilities.
Paul and David updated the group on the progress that has happened since the last meeting and explained the different stages of the project. With the help of two Fighting Blindness supported clinicians, Dr Emma Duignan and Dr Tahira Saad, over 600 Irish people are now part of this growing project. Giuliana gave an overview of her continued efforts in Northern Ireland to characterise the population of NI and expressed her delight in teaming up with David and Paul on developing an all-Ireland register of inherited retinal disease. Matthew gave an overview of the huge technical challenges that he faces in managing the data generation that such a project produces, and the procedure through which candidate genes can be identified that may be causative for a condition. The discussion ended with a ‘call to action’ for anyone who has not yet signed up for Target 5000, but would like to get involved, to contact Fighting Blindness on 01 6789 004 or email@example.com for more information.
We were pleased to host condition-specific breakout sessions in the following areas:
- age-related macular degeneration
- retinitis pigmentosa
- Usher syndrome
- other inherited conditions
In these groups an Irish doctor, an Irish scientist and some of our international experts answered very specific questions that people had about their own condition. There were some excellent questions in each session, generating important and insightful discussions between experts and patients.
National Vision Coalition
This year has seen some incredible strides being made at policy development and healthcare delivery levels as Fighting Blindness has been a driving force within the strong National Vision Coalition. We were pleased to have consultant ophthalmologist Mr David Keegan from the Mater Hospital to give specific updates on the progress of the coalition and future plans to ensure the implementation of a National Vision Strategy.
To have patient organisations and service users directly involved and leading this process is an enormously positive position in ensuring that patient needs and benefit are informing these high level decisions which will affect our members. A broad and energetic discussion around this topic at the conference has provided valuable feedback for the coalition to work with and we urge people to get in touch to discuss these aspects of advocacy with us and to get involved.
An incredibly potent time during the meeting centred around the encouraging, moving and deeply personal account that was shared by Fighting Blindness member Carol Brill. Carol bravely shared her own story of living with Usher syndrome, a condition which results in retinitis pigmentosa and associated hearing loss. Carol spoke about the challenges she has faced and overcome. Her empowered attitude to live every day as a gift was appreciated by every person attending and we are grateful to Carol for sharing so gracefully and eloquently.
The Retina 2014 Conference was officially closed Ms Christina Fasser, President of Retina International.
Thank you to all our speakers, guests and all those who contributed to Retina 2014. Please click here to download the full Retina 2014 Conference Programme. For further details about any of the above, please contact firstname.lastname@example.org or 01 6789 004.
Retina 2015 will take place in Croke Park, Dublin, on Friday, November 6 and Saturday, November 7 2015.