Systemic Bevacizumab (Avastin) Therapy for Neovascular Age-Related Macular Degeneration: Twenty-Four–Week Results of an Uncontrolled Open-Label Clinical Study
Presented in part at: American Society of Retinal Specialists Annual Meeting, July 2005, Montreal, Canada; Retina Society Annual Meeting, September 2005, San Diego, California; and American Academy of Ophthalmology Annual Meeting, October 2005, Chicago, Illinois.
Received 28 October 2005; accepted 30 May 2006. published online 05 October 2006.
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).
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 μm (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 bevacizumab 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.
1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
3Division of General Medicine, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, Florida.
Correspondence to Philip J. Rosenfeld, MD, PhD, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 N.W. 17th Street, Miami, FL 33136.
Manuscript no. 2005-1037.
Supported by the Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida; an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York; the Ronald G. Michels Fellowship Foundation, Riderwood, Maryland; and the German Research Foundation, Bonn, Germany.
No financial support was received from Genentech, Inc. to perform this clinical study, and no support was received for scientific presentations at meetings and travel expenses related to this clinical study. All potential conflicts of interest relate to competing drugs and pharmaceutical companies. Dr Rosenfeld has received competing clinical research grants from Genentech, Inc., Eyetech Pharmaceuticals, QLT, Inc., Novartis Ophthalmics, and Alcon Laboratories and has served on a speaker’s bureau for Novartis Ophthalmics. Drs Rosenfeld and Puliafito have indicated support for competing scientific presentations at meetings and reimbursement for travel expenses. Drs Moshfeghi, Rosenfeld, Puliafito, and Michels have participated in competing scientific advisory boards and have received honoraria and reimbursement for travel expenses. Dr Puliafito is designated on a patent for optical coherence tomography and receives royalties.
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