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Surgeon: VEGF inhibition is new treatment paradigm for CNV
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PITTSBURGH — Treatment of choroidal neovascularization is undergoing a shift to “a new treatment paradigm,” according to a retinal surgeon speaking here.
Carmen A. Puliafito, MD, MBA, spoke about molecular therapy for CNV at a symposium on “Angiogenesis and its inhibition” here at the University of Pittsburgh Medical Center.
Dr. Puliafito said that molecular therapy is directed at a validated target, vascular endothelial growth factor (VEGF), and that treatment of retinal diseases will benefit from this approach to therapy.
“There may be other biologic targets for the treatment of CNV, but we know that in the late stages of the disease … the most relevant biologic molecule at work is VEGF. We may really be looking at a unitary treatment approach against all major vascular complexes,” he said. “Retinal pharmacotherapy radically changes the way that we look at retinal disease and retinal therapy.”
Dr. Puliafito also spoke about the use of optical coherence tomography to evaluate retinal disease management with VEGF inhibition. He said OCT has to date allowed researchers to document retinal changes following treatment with photodynamic therapy using Visudyne (verteporfin for injection, Novartis/QLT), Dr. Puliafito said.
But he said drug treatment may be preferred to PDT in years ahead because it may be that PDT causes collateral damage to photoreceptors, which could affect the preservation of visual function. Conversely, drug therapy may produce “rapid and dramatic changes” to retinal disease structures, he said.
No matter the treatment modality, visual acuity will remain the main endpoint in re-treatment decisions, he said. But an objective test showing a secondary endpoint is also necessary to aid re-treatment decisions.
“And that endpoint, I think, will be optical coherence tomography,” Dr. Puliafito said. “OCT will be the main objective test for making anti-VEGF re-treatment decisions. OCT is a way of looking at these eyes and predicting disease recurrence prior to symptomatic vision loss in some cases.”
During early clinical trials of anti-VEGF compound Lucentis (ranibizumab, Genentech), early re-treatment of some patients was done before vision loss occurred, when significant blood vessel leakage was identified with OCT, Dr. Puliafito said.
“What we needed to see on OCT was an increased thickness greater than or equal to 100 µm, accumulation of subretinal blood, or a more active disease state,” he said.
Results from trials of Macugen (pegaptanib sodium injection, Eyetech Pharmaceuticals) and Lucentis also indicate that some patients may not require continued re-treatment with the anti-VEGF drugs, Dr. Puliafito noted.
“I think there is something happening with the anti-VEGF effect in some eyes where there is a breaking of the vicious circle of continuing activation and secretion of VEGF, which is induced by injections of agents such as Macugen and Lucentis,” he said. “Long-term inhibition of VEGF in eyes with choroidal neovascularization may not be such a bad thing after all.”