Elsevier

Ophthalmology

Volume 112, Issue 6, June 2005, Pages 1035-1047.e9
Ophthalmology

Original article
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.
https://doi.org/10.1016/j.ophtha.2005.02.007Get rights and content

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).

Design

Open-label, single-center, uncontrolled clinical study.

Participants

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.

Section snippets

Patients and Methods

Approval for the SANA Study was obtained from the institutional review board/ethics committee at the University of Miami School of Medicine. The SANA Study will observe patients for at least 1 year after enrollment. Informed consent was obtained from all patients before determination of full eligibility (Table 1), and this research was compliant with the Health Insurance Portability and Accountability Act of 1996. At the start of this study, eligible eyes were designated study eyes, and if both

Baseline Characteristics

A total of 15 patients were initially screened, and 6 patients were excluded from the study for the following reasons: 4 had vision better than 20/40, 1 had uncontrolled hypertension, and 1 had a history of ischemic heart disease. The first 9 patients enrolled in the study had a mean age of 78 years and a median age of 80 years (range, 71–89), with 8 women and 1 man enrolled. All 9 patients completed the 10 visits scheduled for the first 12 weeks of the study. The types of subfoveal neovascular

Patient 1 (Figures 6–8)

An 89-year-old woman was complaining of vision loss in her left eye (study eye) after a single treatment with PDT. Three months after PDT, she was diagnosed with a large submacular hemorrhage in association with leakage from subfoveal occult CNV (study eye; Figs 6A, 7A, 8A). The lesion in the right eye (fellow eye) was diagnosed as a fibrotic scar with an area of active CNV in the temporal macula. At baseline, BCVAs were 20/80+1 in the study eye and 20/500 in the fellow eye. Central retinal

Discussion

After 3 months, the results from the SANA Study are promising but also very preliminary. In this first cohort of 9 patients receiving 2 or 3 infusions of bevacizumab at a dose of 5mg/kg, systemic bevacizumab was associated with a significant increase in VA and a significant decrease in central retinal thickness as early as 1 week after initiation of therapy. This overall improvement continued through week 12 of the study. Because 8 of the 9 patients had evidence of CNV in both eyes, we expected

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    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.

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