16th RETINA INTERNATIONAL CONGRESS Stresa, Italy 22nd to 28th June 2010

Congratulations to RETINA ITALIA ONLUS, the organizers of the 16th Retina International Biennial Congress held in the beautiful town of Stresa on the banks of Lake Maggiora in northern Italy. Representing South Africa were National Chairman James Cape, his wife Sandra and Director for Science Claudette Medefindt. The Congress format was 2 meetings of the Management Committee of RI, a one day continuing Education Program, a one day General Assembly of RI and 2 days of the main congress.

At the Management Committee meeting your editor was proud to accept the nomination as Deputy President of Retina International with the portfolio of membership development. This is a huge challenge but very critical to ensure that successful clinical trials are converted to treatments that will be available to all retinal patients, world-wide. The General Assembly adopted a major constitutional amendment to move from country-based membership to organization-based membership. This will allow for more than one member from a single country and has special significance for multi language and multi cultural countries with huge populations such as China. Four new candidate members were accepted: Retina India, FARP from Argentina, Retina Pigmentosa ASBL from Belgium, and Taiwan RP Association. Fundalu RP from Chile was accepted as an interested Organization.

The main congress, held over 2 days, was very exciting with excellent presentations from the cream of international retinal researchers. There were 62 presentations in 3 parallel sessions attended by 600 participants from 23 countries. I attended the plenary and scientific sessions and cannot hope to give a summary of all the papers. I will however borrow liberally from Professors Chader and Hollyfield who gave excellent summaries at the end of the conference, add some of the highlights and leave you with some quotable quotes.

PROFESSOR GERRY CHADER

Prof Chader is the Secretary of the Retina International Scientific Advisory Board and also a member of Retina SA SMAB. Professor Chader was given a certificate of recognition from Retina International at the congress.

Professor Chader explained that there are 2 distinct categories for therapy in Retinal Regeneration [RD].

Where no photoreceptor [PR] cells survive and replacement of the cells or cell function is needed.

Where some PR cells survive and we need to rescue PR cells and prolong their viability.

REPLACEMENT 1. ELECTRONIC DEVICES - THE ARTIFICIAL RETINA:

 

• Prof Zrenner from Germany reported on the progress of the retinal implant from Retina AG. The Micro Chip is 3mm in Diameter and 50 Dm thick. There are 1500 photo-diodes in the chip which is implanted below the retina. The microprocessor is implanted behind the ear and the connection to the power supply on the belt is wireless. Professor Zrenner reported on 12 patients who had successful outcomes. These included the reading of large letters [4cm] and the combining of these into words, the successful distinguishing of various articles such as a cup, spoon, fruit etc. The video also showed a patient successfully detecting 2 people in a room and identifying the smaller one. Professor Zrenner has agreed to the inclusion of South African patients in the trial but the criteria is strict- RP patients with light perception only. Around 4 trips to Germany will be for the patient’s cost but the treatment will be free. Contact the national office for more details. Professor Zrenner is co-chair of the RI SMAB and was also given a certificate of recognition at the congress.
  
   
• Second Sight was not reported on at the RI congress but at the ARVO conference held in the USA in May. Multi centre trials involving 32 patients in 11 centres were reported on. After implantation of the Argus 2 device patients could locate a door, walk on a white line and correctly detect a square on an LCD screen.
  
  2. STEM CELLS:
  
  Professor Robin Ali reported that Photo Receptors and Visual function HAD been restored in Mouse model of RD using embryonic Stem cells. This was demonstrated by a video of swimming mouse models correctly identifying a safe platform identified by a visual screen. The mice found the platform more than 70% of the time and also had improved visual ERG responses. The research was in very preliminary stages as the therapy only worked in young mice and a more appropriate source of cells was needed. They also needed to improve the number of cells that integrated into the retinal cells.
  
  Professor Ali was the first researcher to do human gene replacement therapy in the ongoing clinical trial for Leber Congenital Amauroses –Ed
  
  3. OPTOGENETICS:
  
  Optogenetics is a new field of research and it is the science of controlling the "on-off" state of neurons in other words triggering or stopping certain actions within a cell. In retinal research conferring light sensitive properties on the remnants of degenerating PR cells are being investigated- Optical PhotoSwitches.
  
  A photoswitch is a protein that makes a living cell react electrically to a light signal. In RD although rods and cones die other retinal cells like ganglion and bipolar cells remain.
  
   
• Botond Roska presented his new research which was published in the journal SCIENCE , June 24th 2010. His work features the genetic transfer of Channel Rhodopsin, a light sensitive protein derived from algae, to the remaining cells to create photosensitivity.
  
   
• John Flannery’s work in this area was not reported at the congress but at ARVO and in our previous E-News. His group is using an Adeno Associated Virus [AAV] to deliver the engineered light activated glutamate receptor (LiGluR) to the retina in several different mouse models of RP. The LiGluR successfully integrated into retinal ganglion cell membranes and they detected light responses. This technique is promising for retinal conditions where photoreceptors cells are damaged or degenerated but retinal ganglion cells remain intact.
  
  Prof Chader: "Basic work on Photo-switches is yet at an early stage of development. Some only work at very high and dangerous light intensities. Others work at light wavelengths that could cause retinal damage. Some react to light too slowly to be useful in human vision. However, photoswitches could yet give functional vision if these problems can be overcome".
  
  RESCUE – when some Photo Receptors remain
  
  Treatments that are looking at prolonging the life and function of Rods and Cones:
  
  1. GROWTH FACTORS
  
  Encapsulated Cell Technology to deliver growth factors to the retina. Dr Weng Tao reported on the successful clinical trials by Neurotech to test:
  
   
• the effect of CNTF on RP. There were no changes in Visual Acuity but less cone loss over the period of the trial.
  
   
• the effect of CNTF2 for Dry AMD. The results of a trial of 51 patients were reported. There was an increase in Retinal thickness that was dose dependant. They maintained Visual Acuity while the sham group lost 15 letters. This will probably be the FIRST TREATMENT FOR DRY AMD!
  
  2. VISUAL CELL MODIFIERS
  
  In some conditions, such as LCA the retina is unable produce the retinal form of vitamin A causing photoreceptor cell dysfunction. If retinal can be replenished, the visual process should be restarted and the person should see again.
  
  Pharmaceutical Intervention: Professor Rob Koenekoop from Canada reported on the QLT short term trial to test LCA patients with an oral form of 11- cis- retinal. The trial on 3 patients lasted only 7 days but ALL 3 had improved Visual Acuity and better Quality of Life e.g. improved reading. The improvement continued AFTER the treatment was stopped. A more comprehensive trial is being planned.
  
  3. ANTI OXIDANTS
  
  The importance of nutritional supplements in RD was reinforced by numerous speakers:
  
  Prof Chader- "The use of nutrition in RD has always been controversial. It now must be taken more seriously in prevention or at least slowing down the degeneration. A current clinical trial in Spain shows good results and further trials are planned".
  
  Prof Falsini- "Gene Mutations lead to apoptosis. Anti oxidants seem to rescue cone function and slow the course of cone degeneration but also in functional rescue of the surviving cones."
  
  Prof Theo van Veen "Death of Photoreceptors leads to Hyperoxia and Oxidative stress."
  
  Anti oxidants such as Retina Complex [Retina Plus in South Africa] without doubt offer protection against oxidative stress.
  
  4. GENE THERAPY
  
  Prof Chader- "Gene Replacement Therapy is the replacement of a defective gene in living cells with a new, normal copy of the gene. The new gene will synthesize a missing protein and restore function to the photoreceptor cell. Long-term, positive effects of Gene Therapy in RP animal models have been shown even if treatment is done fairly late in the disease after significant photoreceptor cell loss".
  
  Professor Jean Bennet reported on the Gene replacement therapy in the RPE65 gene for Lebers Congenital Amauroses. All 4 International trials had successfully restored vision but the younger patients had better results. She reviewed 31 patients who had been treated up to 3 years ago. There were 2 adverse events – 1 macular hole and 1 retinal detachment. There was improved vision in 28 patients. New tests were looking at dose escalation and were treating younger patients. They were also looking at treating the 2nd eye at the patient’s request.
  
  5. UPCOMING GENE THERAPY TRIALS
  • Stargardt Dystrophy- the long awaited Stargen project was due to start at the end of 2010. This trial would use a Lento Virus to replace the ABCA4 gene. The company was in the process of manufacturing material and conducting toxicology tests.
  • Another form of Leber Congenital Amaurosis - LCA5, involving the Lebercillan gene was expected to go into clinical trials soon.
  • Usher Syndrome - The Oxford Biomedica Ushstat project also using LV delivery of the MYO7 Gene in Usher Type 1b was also in an advanced stage.
  • MERTK gene for early onset RP- Proof of Principle had been determined and the viral vectors are being produced.
  • Preclinical work on other forms of LCA such as the GUCY2D and RPGRIP1 mutations are moving towards clinical trials.
  • Retinoschises - This is an X linked condition where the Retina splits. The company AGTC is testing gene therapy in primate models but intricate surgical issues need to be resolved.
  • Achromotopsia - The delivery of genes using Adeno Associated Virus [AAV] is being investigated in 3 genetic subtypes- the GNAT2, CNGA3, CNCB3 in 2 mouse models and 1 dog model. The Visual Acuity, contrast sensitivity and cone survival all improved.
  
  6. SYSTEMIC DRUG DELIVERY
  
  An efficient and safe way to deliver beneficial agents to the retina is prevented by the natural Blood/Retina barrier. Professor Peter Humphries from Trinity College Ireland has achieved promising results in the opening of this barrier to deliver therapeutic agents to suppress Apoptosis, protein mis-folding and neovascularisation. This research is very new and tremendously promising
  
  AGE RELATED MACULAR DEGENERATION
  
  
  
  Excellent papers on AMD were given by numerous speakers including Professors Joe Hollyfield, Alan Bird and Johanna Seddon. Professor Joe Hollyfield is the co-chair of the RI SMAB and was also presented with a recognition certificate for RI. Professor Alan Bird pictured here with James and Sandra Cape admitted that retirement was not an option at this time, with all the exciting advances in retinal research.
  
  The undisputable facts that emerged from the congress are that Nature and Nurture combine in AMD, in that genetics play a significant role and environmental factors combine with genetics. Patients over the age of 55 are at risk and that Drusen are present early in the disease. Certain factors are un-modifiable such as age and genetics but other important factors are modifiable such as diet, supplementation, smoking, body mass index, cholesterol levels and hypertension. Professor Seddon advised AMD patients to include in their diet:
  • A serving of Spinach 5 to 6 times per week
  • Oily fish 3 times per week to ensure adequate Omega 3 fatty acid
  • Foods rich in Vitamin D, E and C
  • And to drink Green tea, high in anti oxidants
  Quit Smoking!!
  
  Smoking 25 cigarettes per day increases your risk of AMD to 2,4 times the norm and that risk only decreases to 2 times after 20 years.
  
  
  
  "Associations between genes and modifiable factors like diet and supplements, smoking, and body weight have shown that these factors can alter genetic susceptibility, and together they can predict AMD" - Dr Johanna Seddon.
  
  TREATMENTS FOR AMD
  
  The results of the head to head trial of Lucentis and Avastin for the treatment of Wet AMD would be available at the end of 2010 and are eagerly awaited.
  
  Around 700 other treatments were under investigation such as:
  • Retinostat to deliver Antivascular genes Angiostatin and Endostatin for AMD and Diabetic Retinopathy
  • VEGF TRAP
  • ACU 4429 inhibitor for dry AMD
  • Pazopanib Drops for Wet AMD
  
  QUOTABLE QUOTES
  
   
• Inherited retinal diseases constitute the major cause of visual impairment and blindness in children and young adults in the western world. Their aggregate prevalence is 1 in 2,000 individuals - Frans Cremers
  
  AAV administration was well tolerated and each of the subjects showed sustained improvement in subjective and objective measures of vision. Several subjects are no longer legally blind. The greatest improvement was observed in children, all of whom gained ambulatory vision - Dr Jean Bennet
  
   
• Oxidative stress mechanisms play a crucial role in neurodegeneration, research using free radical trappers/scavengers, including combinations of anti oxidants, have been shown to delay photoreceptor cell death in several animal models for RP, and soon, a human clinical study will be completed -Theo van Veen
  
   
• Barrier modulation has been used to protect the retinas of mice against light damage, to restore visual function and to suppress misfolding and aggregation of mutant proteins in a model of autosomal dominant RP, in all cases by systemic drug treatment - Professor Pete Humphries
  
   
• These results indicate that RdCVF can not only partially rescue cones but also significantly preserve their functional activity, thereby demonstrating the potential of RdCVF for preserving vision in patients. - Jose Sahel
  
   
• Intraocular CNTF delivered by ECT produced long-term increased retinal thickness and stabilized visual acuity, without serious adverse events, in eyes with geographic atrophy associated with nonneovascular AMD - Dr Weng Tao
  
  
  
  Dr Weng Tao pictured with Prof Gerry Chader
  
   
• Recent studies have shown that transplantation of photoreceptors can result in an improvement in visual function in mouse models of retinal degeneration and that it is possible to generate photoreceptor cells from embryonic stem cells – Prof Robin Ali.
  
  
  
  Pictured at the RI congress are Professor Joe Hollyfield and his wife Dr Mary Rayborn with Claudette Medefindt [right]
  
   
• Many individuals (around 70%) with AMD have polymorphisms in genes that code for or are linked to some of the immune systems complement pathway proteins; and that oxidative damage to lipids in the outer retina may be the inflammatory signal from this tissue that targets the immune system to attack the macula- Professor Joe Hollyfield.
  
   
• In summary, much is now known about the inherited retinal degenerations. Specifically, enough is known to demonstrate scientific "Proof of Principle" in RD animal models that such interventions can be both efficacious and safe. Based on this, human Clinical Trials for these diseases are now taking place with many more to come in the next few years.
  
  In the words of Prof Chader –
  
  "Patients and Researchers are a great team to make our dreams come true."
  
  NEW FACES AT RETINA SOUTH AFRICA
  
  
  
  Robert Kershaw has joined RSA as Manager of Marketing, Fund Raising and Special Events. He has a wealth of experience in the marketing field and spent 2 years in Britain with the Royal National Institute for the Blind. Rob is passionate and articulate and his own retinal condition adds to his motivation. We wish him well.
  
  Gwen Vermaak and Beppie Summersgill are two new volunteers at the National office. We thank them for their support of our vision. Can you spare a few hours a week to assist at the national or your branch office? We need your help. We also need storage space in the Johannesburg area of around 9 square meters. Any offers?
  
  WORLD RETINA WEEK SEPTEMBER 20th to 26th
  
  WRW kicks off Eye Care Awareness month in South Africa. Please place posters on AMD or RD in your community. A collection can placed at a retail outlet or your own private Dinner in the Dark will also help bring in much needed funds. Orders or queries to your branch or national Office. We also need volunteers to man the phones at the National Office.
  
  ARVO REPORT
  
  A copy of the report on the ARVO congress prepared by Dr Elaine Richman for Retina International is available on request.
  
  SCREEN READING SOFTWARE By Duncan McAllister
  
  Being partially sighted I used to think that screen-reading software was only for the totally blind. A large monitor helped but it still took ages to read documents. A blind colleague suggested that I give Jaws a try, and as my employer was upgrading all blind employees to Jaws 11, I jumped on the bandwagon. What a difference, what used to take me an hour to read now takes 15 minutes. Two documents totaling 50 pages took me only 90 minutes to read. I am still learning to use the program and will become even more efficient in time. I reckon I can read as fast, if not faster than a sighted person with this software. When starting it’s best to set the voice speed to a fairly slow pace, but after awhile your brain will adapt, and then you can speed it up.
  
  For those who cannot afford the hefty price tag of Jaws, you can download free software by NVDA. It’s very simple to download and install, and works reasonably well. In fact it even reads icons and toolbars out loud when you mouse over them, something Jaws does not do. They even have a version which you can place on a memory stick that enables you to activate text-to-speech on any computer without installing the software on that computer.
  
  Deductibility of medical and disability expenditure and the visually impaired – How much can you claim? What are the criteria for being classified as having a disability? For the full article provided by Duncan McAllister please send a request to national@rpsa.org.za.
  
  Duncan received a rare accolade from the Tax guru Matthew Lester in his Sunday Times column recently. Lester, a professor at Rhodes University praised Duncan on his knowledge of Capital Gains Tax- The editor.
  
  NEW WEBSITE
  
  We’re live with our new upgraded website thanks to the generous sponsorship of Simon Cleminson at Maxxess Solutions (Pty) Ltd. We have a sparkling new look and a new web address (www.retinasa.org.za) but the old web page will still link through to the new one.
  
  Maxxess Solutions (Pty) Ltd provides cost effective specialized business solutions to mainly SME’s (small to medium enterprises) by taking advantage of the wealth of technologies and services emanating from the information Technology and Mobile Technology Business Sectors. Services include items such as specialized software development, ongoing software support, computer infrastructure and network design, support and installation, application and infrastructure hosting services as well as Internet Services such as Internet Site construction, hosting, e-mail services and dial-in facilities.
  
  For more information please do not hesitate to contact Maxxess Solutions.
  
  'ALLO 'ALLO
  
  A live show of the popular TV series was held in Kempton Park on Saturday 31st July. Thanks to the excellent cast and management of KATS theatre group, all those who attended and our sponsors: Scooters Pizza, Forever Resorts and Tiger Brands Snacks, Treats and Beverages. Over R10 000 was raised for Retinal Research.
  
  Retina South Africa would like to thank Novartis for their generous sponsorship of the costs of Claudette Medefindt to attend the Retina International Congress.
  
  
  
  The production and distribution of this newsletter was sponsored by Novartis (www.novartis.com).
  
  Please update your records via Email to national@rpsa.org.za, telephone 0860 595959 or fax to +27 11 6226277. It is vitally important that members keep their details up to date – especially eMail addresses – in order for Retina SA to keep members informed of research developments and of course for the distribution of the eNews.
  
  
  
  The National Lottery Distribution Trust Fund supports Retina South Africa.