Current understanding of pathogenesis of dry AMD still unsatisfactory
New stem cell treatment approaches entering clinical studies
“Despite recent advances in the imaging of dry age-related macular degeneration (AMD), current understanding of its pathogenesis is still unsatisfactory,” said Lyndon da Cruz MD at the XXXIV Congress of the ESCRS in Copenhagen, Denmark.
Prof da Cruz, Moorfields Eye Hospital, London, UK, outlined five broad etiological categories: oxidative damage; accumulation of toxic visual cycle products; chronic inflammation involving complement activation; choroidal vascular insufficiency; and neurological damage. All of these lead to retinal pigment epithelium (RPE) and photoreceptor cell loss, which provides a target for treatment modalities.
“Potential treatment strategies involve replacing either the function of the cells, or the cells themselves,” he said.
Previous treatment modalities have included macular translocation and autologous RPE graft transplantation. “These techniques have produced some very good results, in wet degeneration, but they involve complex operations with potentially serious complications and thus poor risk-benefit ratio for all but the most severe cases,” said Prof da Cruz.
Considering the age of the patients who are affected, as well as the number of patients who need to be treated, a simpler, lower-risk transplant that can be performed earlier in the disease process is needed, he said.
Prof da Cruz believes the future of dry AMD treatment lies in stem cells. He familiarised delegates with the technique developed by him and Prof Pete Coffey at UCL, of inducing embryonic stem cells to differentiate into mature RPE tissue. This takes place on a relatively stiff, 10-micron-thick membrane. This RPE-laden membrane is then preloaded into an injector and inserted under the retina via a transretinal, parafoveal incision in patients with macular degeneration.
“What we are working towards is based on the cataract surgery model, with a preloaded transplantation patch populated with an easily accessible cell source,” he said.
What we are working towards is based on the cataract surgery model, with a preloaded transplantation patch populated with an easily accessible cell source
A large trial with a porcine model has been completed, and a phase I trial has begun in Moorfields Eye Hospital. “Previous RPE transplantation or macular translocation techniques have always used ‘old’ RPE,” said Prof da Cruz. “Here, we’re placing the overlying retina on brand new RPE. This is what we mean when we talk about regenerative medicine.”
Prof da Cruz showed optical coherence tomography images of a successfully placed subretinal RPE patch with a very normal-appearing retina, including a near-physiological foveal depression, overlying it. The images seemed to give hope to delegates that they might some day be able to offer their patients a beneficial treatment option for dry AMD.
Lyndon da Cruz: firstname.lastname@example.org