Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration - Twenty-four-week results of an uncontrolled open-label clinical study

Purpose: To evaluate the safety, efficacy, and durability of bevacizumab for the treatment of subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD). Design: Open-label, single-center, uncontrolled clinical study. Participants: Age-related macular degeneration patients with subfoveal CNV (n=18) and best-corrected visual acuity (VA) letter scores of 70 to 20 (approximate Snellen equivalent, 20/40-20/400). Methods: Patients were treated at baseline with an intravenous infusion of bevacizumab (5 mg/kg) followed by 1 or 2 additional doses given at 2-week intervals. Safety assessments were performed at all visits. Ophthalmologic evaluations included protocol VA measurements, ocular examinations, and optical coherence tomography (OCT) imaging at each visit. Retreatment with bevacizumab was performed if there was evidence of recurrent CNV. Main Outcome Measures: Assessments of safety and changes from baseline in VA scores and OCT measurements were performed through 24 weeks. Results: No serious ocular or systemic adverse events were identified through 24 weeks. The only adverse event identified was a mild elevation of mean systolic and diastolic blood pressure measurements (+11 mmHg, P=0.004; +8 mmHg, P < 0.001) evident by 3 weeks and easily controlled with antihypertensive medications. By 24 weeks, the systolic and diastolic mean blood pressures were at or below baseline measurements. Visual acuity in the study eyes improved within the first 2 weeks, and by 24 weeks, the mean VA letter score increased by 14 letters in the study eyes (P<0.001), and the mean OCT central retinal thickness measurement decreased by 112 mu m (P<0.001). By 24 weeks, retreatment was needed for only 6 of the 18 study eyes, and after retreatment, the recurrent leakage was eliminated, with restoration of any lost VA. Conclusions: Systemic bevacizumab therapy for neovascular AMD was well tolerated and effective for all 18 patients through 24 weeks. By 6 months, most patients did not require any additional treatment beyond the initial 2 or 3 infusions. Despite these impressive results, it is unlikely that systemic bevacizurnab will be studied in a large clinical trial because of the potential risks associated with systemic anti-VEGF therapy and the perception that intravitreal therapy is safer. (c) 2006 by the American Academy of Ophthalmology.