INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR RADIATION RETINOPATHY 53 YEARS AFTER TREATMENT OF RETINOBLASTOMA Stephen J. Kim, MD, G. Baker Hubbard, III, MD
Purpose: To report the successful treatment of rubeosis and an atypical polypoidal vascular lesion in a case of radiation retinopathy treated with intravitreal bevacizumab. Methods: A 56-year-old woman with a history of retinoblastoma treated with radiation in the right eye was followed up for a progressively enlarging lesion in the macula that was associated with subretinal fluid. The patient was examined with serial ultrasound and clinical examinations and underwent pupilloplasty on the right eye to improve the view to her fundus. Fluorescein angiography revealed a vascular lesion with prominent saccular dilations. Her subsequent course was complicated by a retinal vein occlusion, rubeosis, and decreased vision. Results: A single treatment with intravitreal bevacizumab resulted in regression of the rubeosis and atypical polypoidal vascular lesion and subjective improvement in vision, which persisted for 3 months. Conclusion: Rubeosis and atypical polypoidal neovascularization are known complications of radiation retinopathy, and treatment with intravitreal bevacizumab may be beneficial. RETINAL CASES & BRIEF REPORTS 1:198 –201, 2007
treatment with intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA).
From the Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.
R
adiation retinopathy was first documented over one half century ago and is associated with endothelial cell loss, telangiectatic vascular changes, and capillary occlusion.1 The condition has been observed after charged-particle radiation, radioactive plaque or seed therapy, or external beam irradiation.2 Atypical polypoidal neovascularization and rubeosis are known complications.3,4 We describe the late appearance of rubeosis and an atypical polypoidal vascular lesion (PVL) in a patient with radiation retinopathy 53 years after treatment for retinoblastoma who responded to
Case Report A 56-year-old woman with a history of bilateral retinoblastoma, diagnosed at 19 months of age, was treated in the right eye with radiation in 1953. The left eye was enucleated. She was followed at the Emory Eye Center (Atlanta, GA) and in 2003 underwent serial ultrasound imaging to evaluate changes in vision with an enlarging macular lesion associated with subretinal fluid (Fig. 1). Because of a miotic pupil, which severely limited the view to the fundus, and diagnostic uncertainty, she underwent pupilloplasty in 2005. Examination afterward revealed a vascular lesion associated with prominent saccular dilations (Fig. 2), and fluorescein angiography demonstrated mild hyperfluorescence (Fig. 3). Visual acuity remained stable at 20/200 until 2006 when she had sudden decreased vision. She was diagnosed with a retinal vein occlusion (Fig. 3), and her subsequent course was complicated by progressive retinal ischemia, declining vision to counting fingers, and rubeosis. She was treated with 1.25 mg of intravitreal bevacizumab with complete resolution of rubeosis and regression of an atypical PVL (Fig. 4). Vision remained counting fingers, but she reported subjective improvement in vision right after treatment, which persisted at 3 months of follow-up.
Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. (New York, NY [to G.B.H.). G.B.H. is a paid consultant for Genentech, Inc. (South San Francisco, CA), and Theragenics Corporation (Buford, GA). None of the authors have proprietary interest related to the content of this report. Reprint requests: Stephen J. Kim, MD, 1365 B Clifton Road, NE, Suite B3410, Atlanta, GA 30322; e-mail: [email protected]
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Fig. 1. B-Scan ultrasound images of the right eye showing an enlarging macular lesion. Left, Ultrasound image taken on July 1, 2003, demonstrates the macular lesion (white arrow) with associated subretinal fluid (black arrow). Right, Ultrasound image taken on August 25, 2004, demonstrates enlargement of the macular lesion (white arrow).
Discussion Radiation retinopathy has been associated with atypical choroidal neovascularization. Spaide et al3 reported a case of atypical choroidal neovascularization that resembled polypoidal choroidal vasculopathy. The clinical and angiographic appearance of this lesion also resembled polypoidal choroidal vasculopathy and, like their case, was present in an area with sparse choroidal vessels due to previous radiation. The choroidal circulation, like the retinal circulation, is profoundly affected by radiation, resulting in vascular occlusion, remodeling, and ischemia. The late complication of an atypical PVL in this case of retinoblastoma, one half century after treatment with
radiation, is unusual and was likely mediated by vascular endothelial growth factor, because it responded rapidly to treatment with bevacizumab. Bevacizumab is a humanized recombinant antibody that binds all isoforms of vascular endothelial growth factor. Avery et al5 recently reported successful treatment of retinal and iris neovascularization secondary to proliferative diabetic retinopathy with intravitreal bevacizumab. Consequently, we have also been treating iris neovascularization, in cases of neovascular glaucoma and proliferative diabetic retinopathy, with intravitreal bevacizumab with successful regression of the neovascularization and no observed toxicity. Although there is no established treatment for radi-
Fig. 2. Radiation retinopathy with polypoidal vascular lesion. Left, Composite photograph of the right eye taken after pupilloplasty illustrates the macular lesion (black arrow) documented by ultrasound imaging. Right, Closer view of the lesion (within black box) reveals prominent saccular dilations.
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Fig. 3. Early-phase (left) and late-phase (right) fluorescein angiograms show minimal hyperfluorescence (arrows) consistent with low flow through the polypoidal vascular lesion.
ation retinopathy associated with polypoidal neovascularization, the presence of rubeosis prompted us to use bevacizumab. There was not only resolution of the rubeosis with the injection but also almost complete disappearance of the PVL. There is overwhelming scientific evidence supporting the role of vascular endothelial growth factor in initiating and promoting choroidal neovascularization.5 The rapid resolution of the PVL and rubeosis in this case after intravitreal bevacizumab treatment supports the role of vascular endothelial growth factor in mediating complications of radiation retinopathy. Moreover, the late appearance of this lesion and rubeosis reminds us of the possibility of continued
remodeling and ischemia of the retina and choroid years after radiation treatment. Therefore, treatment of radiation retinopathy associated PVL with intravitreal bevacizumab may be beneficial and merits further investigation. Finally, it is important to recognize the risk of injection for eyes with a history of retinoblastoma. However, in this specific case, the patient had already undergone surgery (cataract surgery and pupilloplasty), and there was no clinical evidence of recurrent retinoblastoma. Key words: radiation retinopathy, polypoidal choroidal vasculopathy, bevacizumab (Avastin), choroidal neovascularization, rubeosis.
Fig. 4. Regression of the polypoidal vascular lesion after treatment with intravitreal bevacizumab. Left, Photograph of the right eye demonstrating retinal hemorrhages and sclerotic blood vessels indicating a vein occlusion (white arrow). The polypoidal lesion is still clearly visible (black arrow). Right, Photograph of the right eye demonstrating rapid regression of the polypoidal lesion (black arrow) after treatment with intravitreal bevacizumab.
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References 1.
2.
Boozalis GT, Schachat AP, Green WR. Subretinal neovascularization from the retina in radiation retinopathy. Retina 1987; 7:156–161. Green WR. Retina. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook. 3rd ed. Vol 2. Philadelphia: WB Saunders; 1985:802.
3.
4. 5.
Spaide RF, Borodoker N, Shah V. Atypical choroidal neovascularization in radiation retinopathy. Am J Ophthalmol 2002; 133:709–711. Brown GC, Shields JA, Sanborn G, et al. Radiation retinopathy. Ophthalmology 1982;89:1494–1501. Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006;113:1695–1705.
Purpose: To report the successful treatment of rubeosis and an atypical polypoidal vascular lesion in a case of radiation retinopathy treated with intravitreal bevacizumab. Methods: A 56-year-old woman with a history of retinoblastoma treated with radiation in the right eye was followed up for a progressively enlarging lesion in the macula that was associated with subretinal fluid. The patient was examined with serial ultrasound and clinical examinations and underwent pupilloplasty on the right eye to improve the view to her fundus. Fluorescein angiography revealed a vascular lesion with prominent saccular dilations. Her subsequent course was complicated by a retinal vein occlusion, rubeosis, and decreased vision. Results: A single treatment with intravitreal bevacizumab resulted in regression of the rubeosis and atypical polypoidal vascular lesion and subjective improvement in vision, which persisted for 3 months. Conclusion: Rubeosis and atypical polypoidal neovascularization are known complications of radiation retinopathy, and treatment with intravitreal bevacizumab may be beneficial. RETINAL CASES & BRIEF REPORTS 1:198 –201, 2007
treatment with intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA).
From the Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.
R
adiation retinopathy was first documented over one half century ago and is associated with endothelial cell loss, telangiectatic vascular changes, and capillary occlusion.1 The condition has been observed after charged-particle radiation, radioactive plaque or seed therapy, or external beam irradiation.2 Atypical polypoidal neovascularization and rubeosis are known complications.3,4 We describe the late appearance of rubeosis and an atypical polypoidal vascular lesion (PVL) in a patient with radiation retinopathy 53 years after treatment for retinoblastoma who responded to
Case Report A 56-year-old woman with a history of bilateral retinoblastoma, diagnosed at 19 months of age, was treated in the right eye with radiation in 1953. The left eye was enucleated. She was followed at the Emory Eye Center (Atlanta, GA) and in 2003 underwent serial ultrasound imaging to evaluate changes in vision with an enlarging macular lesion associated with subretinal fluid (Fig. 1). Because of a miotic pupil, which severely limited the view to the fundus, and diagnostic uncertainty, she underwent pupilloplasty in 2005. Examination afterward revealed a vascular lesion associated with prominent saccular dilations (Fig. 2), and fluorescein angiography demonstrated mild hyperfluorescence (Fig. 3). Visual acuity remained stable at 20/200 until 2006 when she had sudden decreased vision. She was diagnosed with a retinal vein occlusion (Fig. 3), and her subsequent course was complicated by progressive retinal ischemia, declining vision to counting fingers, and rubeosis. She was treated with 1.25 mg of intravitreal bevacizumab with complete resolution of rubeosis and regression of an atypical PVL (Fig. 4). Vision remained counting fingers, but she reported subjective improvement in vision right after treatment, which persisted at 3 months of follow-up.
Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc. (New York, NY [to G.B.H.). G.B.H. is a paid consultant for Genentech, Inc. (South San Francisco, CA), and Theragenics Corporation (Buford, GA). None of the authors have proprietary interest related to the content of this report. Reprint requests: Stephen J. Kim, MD, 1365 B Clifton Road, NE, Suite B3410, Atlanta, GA 30322; e-mail: [email protected]
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Fig. 1. B-Scan ultrasound images of the right eye showing an enlarging macular lesion. Left, Ultrasound image taken on July 1, 2003, demonstrates the macular lesion (white arrow) with associated subretinal fluid (black arrow). Right, Ultrasound image taken on August 25, 2004, demonstrates enlargement of the macular lesion (white arrow).
Discussion Radiation retinopathy has been associated with atypical choroidal neovascularization. Spaide et al3 reported a case of atypical choroidal neovascularization that resembled polypoidal choroidal vasculopathy. The clinical and angiographic appearance of this lesion also resembled polypoidal choroidal vasculopathy and, like their case, was present in an area with sparse choroidal vessels due to previous radiation. The choroidal circulation, like the retinal circulation, is profoundly affected by radiation, resulting in vascular occlusion, remodeling, and ischemia. The late complication of an atypical PVL in this case of retinoblastoma, one half century after treatment with
radiation, is unusual and was likely mediated by vascular endothelial growth factor, because it responded rapidly to treatment with bevacizumab. Bevacizumab is a humanized recombinant antibody that binds all isoforms of vascular endothelial growth factor. Avery et al5 recently reported successful treatment of retinal and iris neovascularization secondary to proliferative diabetic retinopathy with intravitreal bevacizumab. Consequently, we have also been treating iris neovascularization, in cases of neovascular glaucoma and proliferative diabetic retinopathy, with intravitreal bevacizumab with successful regression of the neovascularization and no observed toxicity. Although there is no established treatment for radi-
Fig. 2. Radiation retinopathy with polypoidal vascular lesion. Left, Composite photograph of the right eye taken after pupilloplasty illustrates the macular lesion (black arrow) documented by ultrasound imaging. Right, Closer view of the lesion (within black box) reveals prominent saccular dilations.
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Fig. 3. Early-phase (left) and late-phase (right) fluorescein angiograms show minimal hyperfluorescence (arrows) consistent with low flow through the polypoidal vascular lesion.
ation retinopathy associated with polypoidal neovascularization, the presence of rubeosis prompted us to use bevacizumab. There was not only resolution of the rubeosis with the injection but also almost complete disappearance of the PVL. There is overwhelming scientific evidence supporting the role of vascular endothelial growth factor in initiating and promoting choroidal neovascularization.5 The rapid resolution of the PVL and rubeosis in this case after intravitreal bevacizumab treatment supports the role of vascular endothelial growth factor in mediating complications of radiation retinopathy. Moreover, the late appearance of this lesion and rubeosis reminds us of the possibility of continued
remodeling and ischemia of the retina and choroid years after radiation treatment. Therefore, treatment of radiation retinopathy associated PVL with intravitreal bevacizumab may be beneficial and merits further investigation. Finally, it is important to recognize the risk of injection for eyes with a history of retinoblastoma. However, in this specific case, the patient had already undergone surgery (cataract surgery and pupilloplasty), and there was no clinical evidence of recurrent retinoblastoma. Key words: radiation retinopathy, polypoidal choroidal vasculopathy, bevacizumab (Avastin), choroidal neovascularization, rubeosis.
Fig. 4. Regression of the polypoidal vascular lesion after treatment with intravitreal bevacizumab. Left, Photograph of the right eye demonstrating retinal hemorrhages and sclerotic blood vessels indicating a vein occlusion (white arrow). The polypoidal lesion is still clearly visible (black arrow). Right, Photograph of the right eye demonstrating rapid regression of the polypoidal lesion (black arrow) after treatment with intravitreal bevacizumab.
201
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References 1.
2.
Boozalis GT, Schachat AP, Green WR. Subretinal neovascularization from the retina in radiation retinopathy. Retina 1987; 7:156–161. Green WR. Retina. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook. 3rd ed. Vol 2. Philadelphia: WB Saunders; 1985:802.
3.
4. 5.
Spaide RF, Borodoker N, Shah V. Atypical choroidal neovascularization in radiation retinopathy. Am J Ophthalmol 2002; 133:709–711. Brown GC, Shields JA, Sanborn G, et al. Radiation retinopathy. Ophthalmology 1982;89:1494–1501. Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006;113:1695–1705.
