UNDERSTANDING AND TREATING AGE-RELATED MACULAR DEGENERATION

While anti-VEGF therapy has undoubtedly revolutionised the treatment of age-related macular degeneration (AMD), we are still in the early stages of understanding and treating this and related diseases, said participants in the Amsterdam Retina Debate at the 12th EURETINA Congress “It is a fact that when thermal laser photocoagulation was the only treatment available for wet AMD and even in the era of photodynamic therapy, our patients were going blind,†said Enrico Peiretti MD, assistant professor of ophthalmology, University of Cagliari, Italy.

“Now, with anti-VEGF therapy, we have an intervention that allows many patients to maintain their vision and quality of life for many years. Nevertheless, research has not stopped after obtaining good results with anti-VEGF therapy, and it is continuing on a track to find even better approaches that will allow us to help as many patients as we can.†Tim Jackson MD, consultant vitreoretinal surgeon and senior lecturer, King’s College London, England, UK, also expressed hope for future advances in preventing AMDrelated vision loss based on the abundance of ongoing research in the field.

“There is no question that anti-VEGF therapy was a quantum leap in the management of AMD, but while we’ve come a long way, we are not at the end of the road. That is not a pessimist’s view, however, because I believe we are in an accelerated stage of discovery and development that puts us at the dawn of a very exciting time,†said Dr Jackson. The many shortcomings of anti-VEGF therapy and the lack of any effective treatments for dry AMD speak to the gaps that exist in therapeutic solutions for AMD. Dr Jackson noted that anti- VEGF therapy fails to satisfy many of the criteria of an ideal treatment. While anti-VEGF intravitreal injections may be considered low-risk and are well-tolerated by some patients, the procedure is much less acceptable to others. Furthermore, the efficacy of anti-VEGF intravitreal injections is shorter in duration than desired and is incomplete. Not all patients benefit, and among those who do, efficacy is not always maintained, perhaps because of tachyphylaxis or due to poor compliance with the need for maintenance injections. Dr Jackson noted that treatment cost is another significant drawback of anti-VEGF therapy, and he cited UK costs showing that the resources being spent on a patient with AMD are approximately equivalent to having hip replacement surgery every six months. In addition, the treatment burden is high. Projecting that the average patient would continue treatment for 13 years and considering the growing numbers of patients who will become candidates, indicates that intravitreal anti-VEGF injections for wet AMD may not be a sustainable modality in its current form, said Dr Jackson.

Looking ahead

Despite the existing problems with therapy for AMD, consideration of the magnitude and breadth of ongoing research provides reason for optimism. “There is no question that AMD is one of the most dynamic and exciting fields in ophthalmology,†said Dr Jackson. A PubMed literature search shows the number of AMD-related published papers continues to increase. In addition, there are a multitude of therapeutic modalities in the development pipeline, and numerous clinical trials are under way. In preparing his talk, Dr Jackson identified 712 AMD studies on www. clinicaltrials.gov, of which about one-third were actively recruiting patients. These trials, which represent only those registered, are being conducted in multiple countries and encompass a vast array of new approaches to the treatment of wet and dry AMD.

They are evaluating various experimental compounds as monotherapy as well as combinations that may have additive or synergistic activity. The investigational agents represent a variety of novel mechanisms of action and different routes of delivery, including oral and topical. Additionally, there are studies focusing on strategies for optimising dosing regimens for anti-VEGF therapy. The AMD-related research also incorporates studies of retinal prostheses and implantable telescopes, novel approaches to radiation therapy, cell replacement techniques, biologic therapies and gene therapy. Other novel modalities being explored for use in the management of AMD include pharmacologic therapy to relieve vitreomacular adhesion, transcornealdelivered electrical stimulation to increase or restore retinal cell viability, and a “restorative†laser for increasing diffusion through Bruch’s membrane.

Research in the field also includes studies focusing on the role of nutrition in AMD development and progression and to further elucidate AMD pathogenesis and risk factors, including genetic predisposition. “The long list of new drugs being investigated for the management of AMD should convince clinicians of the overwhelming weight of research that is taking place,†said Dr Jackson. Dr Peiretti stated that because AMD pathogenesis is multifactorial, he believes effective prevention and long-term control might depend on a cocktail approach. Application of current and future understanding of the risk factors, including genetics, will be important for proper patient evaluation, early disease detection, and guiding the best intervention, he said.