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Regression of a Subfoveal Choroidal Metastasis of Colorectal Carcinoma After Intravitreous Bevacizumab Treatment
Irene C. Kuo, MD;
Julia A. Haller, MD;
Roque Maffrand, MD;
Ruben H. Sambuelli, MD, PhD;
Victor E. Reviglio, MD, PhD
Arch Ophthalmol. 2008;126(9):1311-1313.
In 2004, bevacizumab (Avastin; Genentech, Inc, South San Francisco, California) received approval by the US Food and Drug Administration for treatment of metastatic carcinoma of the colon or rectum. Approval of bevacizumab for treatment of select cases of nonsquamous, non–small cell lung cancer followed in 2006. Bevacizumab is the first Food and Drug Administration–approved biological therapy designed to inhibit tumor angiogenesis. It targets all isoforms of vascular endothelial growth factor, a diffusible cytokine that promotes angiogenesis and vascular permeability.
Off-label use of intravitreous bevacizumab for potentially blinding ocular neovascular conditions has grown since the first case report in neovascular age-related macular degeneration.1 Its off-label intravitreous use has been described for choroidal neovascularization in pathological myopia,2-3 proliferative diabetic retinopathy,4-7 and neovascular glaucoma.8
We herein describe a patient who was successfully treated with intravitreous injections of bevacizumab for a vision-threatening metastasis of colorectal carcinoma to the subfoveal choroid.
Report of a Case
In August 2005, a 65-year-old woman with proctorrhagia for several months was diagnosed with colorectal adenocarcinoma causing stricture of the sigmoid colon (Figure 1A). Her serum carcinoembryonic antigen level was 16.5 ng/mL (the upper limit of the reference range is 2.5 ng/mL according to the National Institutes of Health Consensus Statement). Her medical history was significant for gastritis and migraine headaches. The tumor was excised, and immunohistochemical staining for vascular endothelial growth factor was demonstrated (Figure 1B). The patient underwent 6 months of chemotherapy with fluorouracil, leucovorin calcium, and oxaliplatin. After treatment, the carcinoembryonic antigen level was 3.2 ng/mL, and the treatment was suspended.
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Figure 1. Computed tomographic scans and immunohistochemical staining. A, A computed tomographic scan with contrast shows carcinoma of the sigmoid colon (asterisk) in August 2005. B, Immunohistochemical staining of excised colon cancer for vascular endothelial growth factor using an avidin-biotin-peroxidase complex technique. Signals were developed for visualization with 3,3'-diaminobenzidine. Brown indicates vascular endothelial growth factor (a few representative areas are denoted by asterisks) (original magnification x400). C, A computed tomographic scan with contrast shows metastasis to the right occipitocortical junction (asterisk) in April 2007.
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In February 2007, the patient had decreasing vision in the left eye. When she was finally examined by an ophthalmologist in April 2007, her visual acuity was 20/20 OD and hand motions OS. On dilated fundus examination of the left eye, a large (approximately 8 x 8-mm), elevated, orange choroidal mass was seen in the temporal posterior pole extending beneath the macula to within 1 disc diameter of the optic nerve. Temporally, the mass had a mottled, yellow-white spotted coloration.
Because the patient also had worsening migraine headaches, her primary care physician obtained a brain computed tomographic scan, which showed a mass in the right occipitocortical junction (Figure 1C). The mass was presumed to be metastatic; her carcinoembryonic antigen level at this time was 28.4 ng/mL.
To avert the risk of intracranial hemorrhage, her oncologists chose to administer radiotherapy rather than chemotherapy to the brain metastasis. The ophthalmologist offered the patient 3 options to address the choroidal metastasis responsible for the loss of vision: implantation of a radiotherapy plaque, enucleation, or intravitreous injection of bevacizumab.
Because the patient was indigent, had no health insurance, and wanted to try to preserve her eye, she chose the least costly medical alternative: intravitreous bevacizumab treatment. Informed consent for this off-label use of bevacizumab was obtained from the patient. Fundus photographs before her first injection in May 2007 (Figure 2A) documented the posterior pole mass. On fluorescein angiography, numerous poorly defined vascular subretinal channels filled quickly but unevenly in the early frames, with some areas of blockage and profuse late hyperfluorescence and leakage. Bevacizumab, 1.25 mg in 0.05 mL, was injected via a 25-gauge needle into the vitreous through the pars plana of the left eye using a standard sterile protocol. Topical antibiotic drops were prescribed for 5 days.
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Figure 2. Fundus photographs and selected fluorescein angiograms of the left eye. A, In May 2007 before an intravitreous injection of bevacizumab. A large, elevated, orange choroidal mass in the temporal posterior pole is noted. On fluorescein angiography, numerous subretinal channels fill quickly in early frames, with profuse late hyperfluorescence and leakage. Visual acuity is hand motions. B, In June 2007, 1 month after the first injection and before the second injection, the mass has shrunk markedly. Fluorescein angiography shows a reduction in tumor mass in all dimensions; early hyperfluorescence appears in a much smaller area than before and fades in the late phases. Visual acuity is 20/40. C, In July 2007, 1 month after the second injection and before the third injection, the tumor mass has almost entirely regressed. Fluorescein angiography documents avascular zones and remodeled patent vessels in the regressed tumor bed without leakage. Visual acuity is 20/30. D, In October 2007, 3 months after the third injection, there is no recurrence of the tumor. The posterior pole has been restored to a normal contour. Fluorescein angiography continues to demonstrate vascular alterations in the choroid with minimal hyperfluorescence. Visual acuity is 20/30.
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Five days after injection, the visual acuity had improved to 20/40. One month after injection, the visual acuity remained 20/40. Marked shrinkage of the tumor mass was appreciated (Figure 2B), such that the central macula was now restored to a virtually normal anatomical appearance. The tumor's nasal extent had receded temporally and was now more than 1 disc diameter lateral to the fovea. Fluorescein angiography further delineated an approximately 50% reduction in tumor mass in all dimensions. Angiographically, the tumor demonstrated early hyperfluorescence in a much smaller area than before treatment, which faded in the late phases consistent with a marked diminution in vascularity and leakage. The patient received a second injection of bevacizumab at this visit.
By July 2007, 2 months after initial treatment, the visual acuity had improved to 20/30 and the tumor mass had almost entirely regressed, leaving confluent yellow-white drusenlike coloration temporally (Figure 2C). Fluorescein angiography documented that focal areas of the former mass, deep to the retinal vasculature, were now avascular with blunted, remodeled patent vessels in the regressed tumor bed; there was no leakage. The patient received a third injection of bevacizumab at this time and refused further injections thereafter.
At last follow-up in October 2007, 5 months after initiating intravitreous therapy, the visual acuity remained 20/30. Fundus examination showed no recurrence of the tumor. The posterior pole of the left eye was restored to a normal contour and appearance with only the yellowish pigmentary mottling remaining in the temporal portion of the previous tumor site (Figure 2D). Fluorescein angiography continued to demonstrate vascular alterations in the choroid, with some areas of attenuation and remodeling and minimal late hyperfluorescence. The patient continued with radiotherapy without systemic chemotherapy for the brain metastasis.
Comment
We report successful short-term regression of a vision-threatening, subfoveal, choroidal metastasis and associated dramatic visual improvement in a patient treated with 3 monthly intravitreous injections of bevacizumab. The presumed mechanisms for the response are the antiangiogenic and antipermeability effects of bevacizumab on the new tumor vessels, and this is supported by the fluorescein angiographic changes. Concomitantly, the mass decreased in size and the patient's visual acuity improved. Alternatives to intravitreous bevacizumab treatment included placement of an episcleral radioactive plaque (with associated operative risks and toxic effects) and enucleation; the less invasive, less expensive therapy given in this case preserved both the vision and the eye. Of course, the long-term success of the treatment remains to be assessed. To our knowledge, there is no other published report of successful induction of intraocular tumor regression with intravitreous bevacizumab treatment.
We chose the injection dosage of bevacizumab used in neovascular age-related macular degeneration; it is possible that a higher dosage would have shrunk the mass further. Intravenous bevacizumab treatment might have addressed both the metastatic colorectal cancer (its first approved indication) and the choroidal metastasis, although the risk of adverse effects (particularly in a patient with a brain metastasis) is much less likely with local injection.
Use of anti–vascular endothelial growth factor agents has opened a panoply of new options for patients with diseases involving the chorioretinal vasculature, and more investigation will be required to elucidate their optimal uses.
AUTHOR INFORMATION
Correspondence: Dr Reviglio, Ophthalmology Research Department, Catholic University of Cordoba, School of Medicine, Molino de Torres 5301, El Bosque, Villa Warcalde, CP: 5021, Córdoba, Argentina (victor-reviglio{at}hotmail.com).
Financial Disclosure: Dr Haller has received research funds from Genentech, has served as principal investigator on Genentech-sponsored studies, and is on the Genentech speakers bureau.
Funding/Support: This work was supported by an unrestricted grant from Research to Prevent Blindness, New York, New York.
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