AMD TREATMENTS

Anti-VEGF therapy has revolutionised the therapeutic approach to neovascular agerelated macular degeneration (AMD) and has opened up potentially exciting avenues for future treatment of the disease, according to Gisele Soubrane MD, PhD, FEBO, FARVO who delivered the annual Kreissig Lecture at the 12th EURETINA Congress. Prof Soubrane, professor of ophthalmology at Hotel Dieu, University Paris Centre Descartes, noted that while important breakthroughs have been made in recent years, the proliferation of recent clinical trials do not provide answers to all the questions physicians face in daily practice.

“While immense progress has been made in recent years, there is still a long way to go in our research. Current treatments are not able to cure AMD and remain palliative in nature. Despite the fact that many of our patients recover some vision, this is only the case in one-third of the treated eyes, and one in every six patients still progress to legal blindness,†she said. Prof Soubrane stressed the importance of finding adapted and appropriate treatment for a disease that will place an increasing burden on national healthcare services in the coming years.

“Forty million people worldwide have AMD of whom 17 million have advanced atrophic or exudative AMD. These numbers are expected to double by 2020,†she said. While upcoming treatments may restrain or even destroy the choroidal neovascularisation underlying the development of AMD, Prof Soubrane said that none of them are foreseen to preclude the occurrence of the neovascularisation in the first place. “A number of key problems remain to be solved. We need to work out the optimal routes of drug or cell delivery and ensure adequate concentration in the target tissue while also sparing the neighbouring tissue,†she said.

With the proliferation of potential treatments now under development targeting different aspects of the pathogenetic cascade chain, Prof Soubrane said that the hope is that these compounds, either alone or in association, may one day lead to an algorithm for personalised treatment. “We still need a better understanding of the pathophysiology of AMD which would lead to earlier intervention to block the cellular and molecular disturbances resulting in the development of CNV in order to tailor new therapeutics,†she said. Among the latest anti-VEGF therapies hoping to compete with ranibizumab, Prof Soubrane noted that both ESBA1008 (Alcon) and AGN150998 (Allergan) are currently undergoing clinical trials to assess their safety and efficacy. Another compound, pazopanib (GSK), has just completed phase 2b trials and could eventually pave the way for a topical treatment for AMD, said Prof Soubrane.

Another interesting approach is the use of integrin antagonists such as Volociximab (Ophthotech) and ALG-1001 (Allegro) that are designed to inhibit endothelial cell proliferation by multiple pathways, said Prof Soubrane. Recent results of the anti-plateletderived growth factor aptamer Fovista (Ophthotech) have also shown considerable promise as an anti-angiogenic treatment when administered in combination with ranibizumab, said Prof Soubane. While much of the research in AMD focuses on new treatments for the disease, Prof Soubrane stressed the importance of learning more about possible predictors of the pathology and which patients might be better responders to current treatment regimens, she said.