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.
"Success in the treatment of dry AMD will be defined by preventing normal disease progression from intermediate high-risk
dry AMD," said Dr Rosenfeld, professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of
Medicine, Miami. "This normal disease progression includes the enlargement of geographic atrophy and formation of choroidal
"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
Dr Rosenfeld showed images from a patient in the PrONTO Study. The patient was treated with 10 injections of ranibizumab (Lucentis,
Novartis) over 2 years, with an improvement in visual acuity from 20/50 to 20/25. Over the following 4 years, during which
time the patient did not receive additional injections, geographic atrophy developed in the centre of the fovea and the visual
acuity decreased to 20/200. This leads to the question: How can we call this a success if the dry AMD continues to progress?
"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."