Systemic Bevacizumab (Avastin) Therapy for Neovascular Age-Related Macular Degeneration: Twelve-Week Results of an Uncontrolled Open-Label Clinical Study
Presented at: Macula Society Annual Meeting, February 25, 2005; Key Biscayne, Florida.
Received 17 December 2004; accepted 9 February 2005.
Purpose
To evaluate the short-term safety of systemic bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA) and its effects on visual acuity (VA) and subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD).
Age-related macular degeneration patients with subfoveal CNV (N = 9) and best-corrected VA letter scores of 70 to 20 (approximate Snellen equivalent, 20/40–20/400).
Methods
Patients were treated at baseline with an 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 and ocular examinations, along with optical coherence tomography (OCT) imaging, fluorescein angiography, and indocyanine green angiography.
Main outcome measurements
Safety assessments were performed, along with assessments of changes from baseline in VA scores, OCT measurements, and angiographic lesion characteristics.
Results
There were no serious ocular or systemic adverse events identified. By 6 weeks, the only adverse event identified was a mild elevation of systolic blood pressure (BP) (+12 mmHg; P = 0.035), and this elevation was controlled by either changing or initiating antihypertensive medication. By 12 weeks, the elevation of systolic BP was no longer significant (P = 0.51). In the study eyes, significant increases in VA were evident within 1 week of treatment, and by 12 weeks, the median and mean VA letter scores increased by 8 letters (P = 0.011) and 12 letters (P = 0.008), respectively. The median and mean central retinal thickness measurements decreased by 157 μm (P = 0.008) and 177 μm (P = 0.001), respectively. In the fellow eyes at 12 weeks, the median and mean VA letter scores increased by 27 letters (P = 0.018) and 16 letters (P = 0.012), and the median and mean central retinal thickness measurements decreased by 59 μm (P = 0.028) and 92 μm (P = 0.06). In all study eyes, angiography revealed a marked reduction or an absence of leakage from CNV.
Conclusion
Overall, bevacizumab therapy was well tolerated, with an improvement in VA, OCT, and angiographic outcomes. Although these preliminary results are promising, a randomized controlled clinical trial is necessary before concluding that systemic bevacizumab therapy is safe and effective for patients with neovascular AMD.
1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida.
2Division of General Medicine, Department of Internal Medicine, University of Miami School of Medicine, Miami, Florida.
Correspondence to Philip J. Rosenfeld, MD, PhD, Bascom Palmer Eye Institute, University of Miami School of Medicine, 900 NW 17th Street, Miami, FL 33136.
Manuscript no. 2004-422.
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; National Institutes of Health, Bethesda, Maryland (center grant no.: P30 EY14801); 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. Drs Rosenfeld and Puliafito have indicated support for competing scientific presentations at meetings and reimbursement for travel expenses. Drs Rosenfeld, Puliafito, and Michels have participated in competing scientific advisory boards and have received honoraria and reimbursement for travel expenses. Dr Rosenfeld has served on a speaker’s bureau for Novartis Ophthalmics. Dr Puliafito is designated on a patent for optical coherence tomography and receives royalties.
Reprint requests to Philip J. Rosenfeld, MD, PhD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136.
1 Dr Michels is currently affiliated with University Eye Hospital Vienna, Vienna, Austria.
ABSTRACT