Novel strategies for testing treatments yield two short-term surrogate endpoints
Novel strategies have been developed to track the progression of dry age-related macular degeneration (AMD) by monitoring the change in geographic atrophy and drusen using spectraldomain optical coherence tomography (SDOCT). Investigators are using these endpoints in clinical trials to test the efficacy of various treatments, said Dr Philip J. Rosenfeld, PhD, during Retina Subspeciality Day at the annual meeting of the American Academy of Ophthalmology.
"These new treatments are desperately needed to preserve vision in patients with dry AMD, but also to maintain the benefits achieved from the use of anti-vascular endothelial growth factor drugs in wet AMD," he added. "We now convert the wet AMD to dry AMD with these drugs, but over time, these patients go on to lose vision gradually from the ravages of the underlying dry AMD."
"In the near future, success will be defined by the preservation of vision," he said. "Perhaps in the far future, we can talk about restoring vision."
Using visual acuity as a clinical trial endpoint is unrealistic because visual loss takes years in AMD, he explained. In addition, vision loss may not be correlated with disease progression and loss of central vision depends on the proximity of the geographic atrophy to the center of the fovea.
"We need a surrogate endpoint that will predict future vision loss," Dr Rosenfeld said. Specifically, in the short term, the endpoint needs to represent a slowing of disease progression, and in the long-term, the endpoint needs to be correlated with vision loss. Glaucoma researchers are familiar with this predicament and that's why they use IOP measurements, the loss of visual field, and the ganglion cell layer as surrogates for vision loss in clinical trials.
"In dry AMD, likely surrogate endpoints include the progression of dry to wet AMD, but [studies designed] with this endpoint would take many years to complete," he said. "It is more realistic to look at the growth of geographic atrophy and decreasing the drusen burden without formation of geographic atrophy or CNV."