Abstract
Purpose: :
An extensive body of research has established that vascular endothelial growth factor (VEGF) is both necessary and sufficient in promoting ocular neovascularization; in addition, it is the most potent known promoter of vascular permeability, and is thus an attractive therapeutic target. Macugen, an RNA aptamer against the VEGF165 isoform, has proved clinically effective as a treatment for all forms of neovascular age–related macular degeneration, as well as for diabetic macular edema In addition, an antibody to VEGF, Avastin, which affords pan–VEGF blockade non–selectively has provided clinical benefit when administered systemically as an adjunct to chemotherapy in cancer patients, though with associated risks of thromboembolic and hemorrhagic complications. Recently, ophthalmologists have experimented with administering Avastin intravitreally as therapy for NV AMD. As the pharmacotherapy of AMD progresses, it is likely that, as seen in oncology, different therapeutic regimens will be employed in combination, as the ideal therapy is searched for. We therefore designed a regimen of combination pulse bevacizumab superimposed upon a foundation of Macugen therapy for treatment of AMD.
Methods: :
Five patients with a cross section of angiographic subtypes of NV AMD and broad range of baseline vision seen in an office based practice were treated with Avastin followed by Macugen administered according to label. Subjects were monitored with formal assessments of visual acuity, slit lamp biomicroscopy, dilated funduscopy, FFA, and OCT.
Results: :
Patients treated with the combination of pan–VEGF blockade with Avastin superimposed upon a foundation of selective VEGF165 blockade afforded clinically meaningful responses as determined by a combined assessment of visual acuity, OCT and FFA ancillary testing.
Conclusions: :
A regimen of pulse pan–VEGF blockade with Avastin superimposed upon a foundation of selective VEGF165 blockade may offer a balance of clinically meaningful outcomes and acceptable safety in the treatment of AMD. Further trials employing combinations of selective and non–selective VEGF blockade seem warranted. Characters 2322
Keywords: age-related macular degeneration • growth factors/growth factor receptors • injection