RADIATION MACULOPATHY COMPLICATED BY INTRARETINAL NEOVASCULARIZATION TREATED WITH INTRAVITREAL BEVACIZUMAB Waheeda Rahman, MRCOphth, FRCS (Ed),* Nachiketa Acharya, FRCOphth,* Mandeep S. Sagoo, MB, PhD, MRCOphth, FRCS (Ed),*† Adnan Tufail, MD, FRCOphth*
Purpose: The purpose of this study was to describe a case of radiation maculopathy as a result of intraretinal neovascularization, treated with intravitreal bevacizumab. Methods: This is an interventional case report. A 51-year-old man was treated with radiotherapy and chemotherapy for nasopharyngeal carcinoma. He developed radiation maculopathy associated with intraretinal neovascularization in the left eye. He underwent a course of 3 intravitreal injections of bevacizumab (1.25 mg/0.05 mL). Results: The visual acuity in the left eye improved with complete closure of the intraretinal neovascularization and no recurrence 17 months after the last bevacizumab injection. Conclusion: This case of radiation-induced intraretinal neovascularization responded well to bevacizumab treatment. These lesions may respond more favorably if treated earlier. RETINAL CASES & BRIEF REPORTS 4:5–7, 2010
From the *Medical Retina Service, Moorfields Eye Hospital; and †UCL Institute of Ophthalmology, London, United Kingdom.
nasopharyngeal carcinoma, treated with intravitreal bevacizumab. Case Report
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adiation retinopathy is a delayed-onset, slowly progressive occlusive retinal microangiopathy,1 which results from radiation exposure during the treatment of ocular, orbital, and cephalic neoplastic and inflammatory disorders. Risk factors for developing retinopathy include large total and fractionated radiation doses, diabetes, and the use of adjunctive chemotherapy. Radiation maculopathy usually presents with telangiectasiae, microaneurysms, capillary occlusion, retinal thickening, or subretinal fluid,1 although subretinal neovascularization has also been described.2,3 We describe the unusual finding of parafoveolar intraretinal neovascularization (IRN) after radiation treatment for
A 51-year-old Chinese man presented with a gradual 2-year reduction of vision in the left eye, 5 years after irradiation and chemotherapy for nasopharyngeal carcinoma. There was no history of diabetes, hypertension, or other associated systemic disease. Visual acuity in the left eye was 6/60, with intraretinal hemorrhage at the fovea and macular edema, which on fluorescein angiography showed a cystoid pattern of hyperfluoresence without a neovascular membrane. The right eye (with visual acuity 6/9) showed macular telangiectasiae, with mild leakage on fluorescein angiography, as shown in Figure 1. After 13 months, left visual acuity was 6/240. There was a marked increase in retinal edema and surrounding exudation. Fluorescein angiography performed with a Heidelberg retina angiograph scanning laser ophthalmoscope and indocyanine green angiography showed the presence of IRN without evidence of choroidal neovascularization and no peripheral ischemia (Figure 1). This was confirmed by optical coherence tomography (OCT, Stratus OCT, Carl Zeiss Meditec, Oberkochen, Germany) as a focal area of hyperreflectivity in the intraretinal tissue associated with edema (Figure 2), but there was no underlying choroidal neovascularization.
The authors have no proprietary interest. Reprint requests: Mandeep S. Sagoo, MB, PhD, MRCOphth, FRCS, Moorfields Eye Hospital, City Road, London EC1V 2PD, UK; e-mail: [email protected]
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Fig. 1. A, Color photograph of the left eye—IRN and severe exudation. B, FFA of the left eye—IRN and leakage without evidence of choroidal neovascularization. C, Indocyanine green of the left eye— hotspot from IRN. D, Color photograph of the left eye 6 months after bevacizumab injections— closure of IRN and reduced exudation. E, FFA of the left eye— closure of IRN 6 months after treatment. F, Indocyanine green of the left eye— closure of IRN 6 months after treatment with inner retinal folds present. G, Color photograph of the left eye 17 months after bevacizumab injections—further reduction of exudation with no recurrence of IRN. H, Color photograph of the right eye—telangiectatic vessels at the macula. I, FFA of right eye—mild leakage of telangiectatic vessels at the macula.
A course of 3 monthly intravitreal injections of bevacizumab (1.25 mg/0.05 mL) was administered after careful discussion and consent of the patient and approval of the local Drugs and Therapeutics Committee to use the drug off-label. The left visual acuity
improved to 4/60 6 months after the last injection, with a subjectively smaller central scotoma. Clinically, there was reduction of the exudation and complete closure of the IRN (Figure 1). Although less macular edema was present on OCT scan, it continued
Fig. 2. Optical coherence tomography scans in the left eye near to the fovea (white arrows: axis of the scans). A, IRN (white arrowhead) and severe edema before treatment. B, Significant reduction of edema 6 months after bevacizumab injections and an associated epiretinal membrane.
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BEVACIZUMAB FOR RADIATION-INDUCED IRN to persist as a result of underlying microangiopathy (Figure 2). There was no recurrence of the IRN and there was further reduction of the exudation 17 months after the last bevacizumab treatment (Figure 1).
Discussion Radiation retinopathy has been associated with a variety of abnormal vascular presentations, but subretinal and choroidal neovascularization have been reported only rarely.2,3 Our case describes an unusual presentation of primarily IRN, similar to lesions previously described as retinal angiomatous proliferation,4 and no evidence of subretinal or choroidal neovascularization. Fluorescein angiography shows an indistinct area of hyperfluorescence but indocyanine green highlights the neovascularization as a focal spot of intense hyperfluorescence. These findings, along with the OCT features (as described previously), support a diagnosis of IRN, a highly unusual presentation in radiation maculopathy. Other possible manifestations of radiation exposure include idiopathic perifoveal telangiectasiae,5 which were noted in the patient’s right eye. Intravitreal bevacizumab (Avastin, Genentech, South San Francisco, CA) is a humanized monoclonal antibody to vascular endothelial growth factor, which inhibits the formation of abnormal blood vessels and decreases vascular permeability. It has been used offlabel intravitreally in the treatment of neovascular age-related macular degeneration and in retinal angiomatous proliferation lesions.6,7 Our case responded favorably to bevacizumab treatment with closure of
the lesion, reduction in macular edema on OCT scan, and improvement in visual acuity in the context of radiation-induced IRN. It will be interesting to see whether IRN lesions in radiation maculopathy are more common than previously thought and whether they respond more favorably if treated earlier. Key words: Avastin, intraretinal neovascularization, intravitreal bevacizumab, macular edema, neovascularization, radiation maculopathy, radiation retinopathy. References 1.
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Archer DB, Amoaku WM, Gardiner TA. Radiation retinopathy— clinical, histopathological, ultrastructural and experimental correlations. Eye 1991;5:239 –251. Boozalis GT, Schachat AP, Green WR. Subretinal neovascularization from the retina in radiation retinopathy. Retina 1987; 7:156 –161. Anzai K, Mori K, Yoneya S. Clinicopathological correlation of a retinal angiomatous proliferation-like lesion in a case of radiation retinopathy. Jpn J Ophthalmol 2006;50:291–293. Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina 2008;28:375–384. Maberley DA, Yannuzzi LA, Gitter K, et al. Radiation exposure: a new risk factor for idiopathic perifoveal telangiectasis. Ophthalmology 1999;106:2248 –2252. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging 2005;36:331–335. Meyerle CB, Freund KB, Iturralde D, et al. Intravitreal bevacizumab (Avastin) for retinal angiomatous proliferation. Retina 2007;27:451– 457.
Purpose: The purpose of this study was to describe a case of radiation maculopathy as a result of intraretinal neovascularization, treated with intravitreal bevacizumab. Methods: This is an interventional case report. A 51-year-old man was treated with radiotherapy and chemotherapy for nasopharyngeal carcinoma. He developed radiation maculopathy associated with intraretinal neovascularization in the left eye. He underwent a course of 3 intravitreal injections of bevacizumab (1.25 mg/0.05 mL). Results: The visual acuity in the left eye improved with complete closure of the intraretinal neovascularization and no recurrence 17 months after the last bevacizumab injection. Conclusion: This case of radiation-induced intraretinal neovascularization responded well to bevacizumab treatment. These lesions may respond more favorably if treated earlier. RETINAL CASES & BRIEF REPORTS 4:5–7, 2010
From the *Medical Retina Service, Moorfields Eye Hospital; and †UCL Institute of Ophthalmology, London, United Kingdom.
nasopharyngeal carcinoma, treated with intravitreal bevacizumab. Case Report
R
adiation retinopathy is a delayed-onset, slowly progressive occlusive retinal microangiopathy,1 which results from radiation exposure during the treatment of ocular, orbital, and cephalic neoplastic and inflammatory disorders. Risk factors for developing retinopathy include large total and fractionated radiation doses, diabetes, and the use of adjunctive chemotherapy. Radiation maculopathy usually presents with telangiectasiae, microaneurysms, capillary occlusion, retinal thickening, or subretinal fluid,1 although subretinal neovascularization has also been described.2,3 We describe the unusual finding of parafoveolar intraretinal neovascularization (IRN) after radiation treatment for
A 51-year-old Chinese man presented with a gradual 2-year reduction of vision in the left eye, 5 years after irradiation and chemotherapy for nasopharyngeal carcinoma. There was no history of diabetes, hypertension, or other associated systemic disease. Visual acuity in the left eye was 6/60, with intraretinal hemorrhage at the fovea and macular edema, which on fluorescein angiography showed a cystoid pattern of hyperfluoresence without a neovascular membrane. The right eye (with visual acuity 6/9) showed macular telangiectasiae, with mild leakage on fluorescein angiography, as shown in Figure 1. After 13 months, left visual acuity was 6/240. There was a marked increase in retinal edema and surrounding exudation. Fluorescein angiography performed with a Heidelberg retina angiograph scanning laser ophthalmoscope and indocyanine green angiography showed the presence of IRN without evidence of choroidal neovascularization and no peripheral ischemia (Figure 1). This was confirmed by optical coherence tomography (OCT, Stratus OCT, Carl Zeiss Meditec, Oberkochen, Germany) as a focal area of hyperreflectivity in the intraretinal tissue associated with edema (Figure 2), but there was no underlying choroidal neovascularization.
The authors have no proprietary interest. Reprint requests: Mandeep S. Sagoo, MB, PhD, MRCOphth, FRCS, Moorfields Eye Hospital, City Road, London EC1V 2PD, UK; e-mail: [email protected]
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Fig. 1. A, Color photograph of the left eye—IRN and severe exudation. B, FFA of the left eye—IRN and leakage without evidence of choroidal neovascularization. C, Indocyanine green of the left eye— hotspot from IRN. D, Color photograph of the left eye 6 months after bevacizumab injections— closure of IRN and reduced exudation. E, FFA of the left eye— closure of IRN 6 months after treatment. F, Indocyanine green of the left eye— closure of IRN 6 months after treatment with inner retinal folds present. G, Color photograph of the left eye 17 months after bevacizumab injections—further reduction of exudation with no recurrence of IRN. H, Color photograph of the right eye—telangiectatic vessels at the macula. I, FFA of right eye—mild leakage of telangiectatic vessels at the macula.
A course of 3 monthly intravitreal injections of bevacizumab (1.25 mg/0.05 mL) was administered after careful discussion and consent of the patient and approval of the local Drugs and Therapeutics Committee to use the drug off-label. The left visual acuity
improved to 4/60 6 months after the last injection, with a subjectively smaller central scotoma. Clinically, there was reduction of the exudation and complete closure of the IRN (Figure 1). Although less macular edema was present on OCT scan, it continued
Fig. 2. Optical coherence tomography scans in the left eye near to the fovea (white arrows: axis of the scans). A, IRN (white arrowhead) and severe edema before treatment. B, Significant reduction of edema 6 months after bevacizumab injections and an associated epiretinal membrane.
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BEVACIZUMAB FOR RADIATION-INDUCED IRN to persist as a result of underlying microangiopathy (Figure 2). There was no recurrence of the IRN and there was further reduction of the exudation 17 months after the last bevacizumab treatment (Figure 1).
Discussion Radiation retinopathy has been associated with a variety of abnormal vascular presentations, but subretinal and choroidal neovascularization have been reported only rarely.2,3 Our case describes an unusual presentation of primarily IRN, similar to lesions previously described as retinal angiomatous proliferation,4 and no evidence of subretinal or choroidal neovascularization. Fluorescein angiography shows an indistinct area of hyperfluorescence but indocyanine green highlights the neovascularization as a focal spot of intense hyperfluorescence. These findings, along with the OCT features (as described previously), support a diagnosis of IRN, a highly unusual presentation in radiation maculopathy. Other possible manifestations of radiation exposure include idiopathic perifoveal telangiectasiae,5 which were noted in the patient’s right eye. Intravitreal bevacizumab (Avastin, Genentech, South San Francisco, CA) is a humanized monoclonal antibody to vascular endothelial growth factor, which inhibits the formation of abnormal blood vessels and decreases vascular permeability. It has been used offlabel intravitreally in the treatment of neovascular age-related macular degeneration and in retinal angiomatous proliferation lesions.6,7 Our case responded favorably to bevacizumab treatment with closure of
the lesion, reduction in macular edema on OCT scan, and improvement in visual acuity in the context of radiation-induced IRN. It will be interesting to see whether IRN lesions in radiation maculopathy are more common than previously thought and whether they respond more favorably if treated earlier. Key words: Avastin, intraretinal neovascularization, intravitreal bevacizumab, macular edema, neovascularization, radiation maculopathy, radiation retinopathy. References 1.
2.
3.
4.
5.
6.
7.
Archer DB, Amoaku WM, Gardiner TA. Radiation retinopathy— clinical, histopathological, ultrastructural and experimental correlations. Eye 1991;5:239 –251. Boozalis GT, Schachat AP, Green WR. Subretinal neovascularization from the retina in radiation retinopathy. Retina 1987; 7:156 –161. Anzai K, Mori K, Yoneya S. Clinicopathological correlation of a retinal angiomatous proliferation-like lesion in a case of radiation retinopathy. Jpn J Ophthalmol 2006;50:291–293. Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina 2008;28:375–384. Maberley DA, Yannuzzi LA, Gitter K, et al. Radiation exposure: a new risk factor for idiopathic perifoveal telangiectasis. Ophthalmology 1999;106:2248 –2252. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging 2005;36:331–335. Meyerle CB, Freund KB, Iturralde D, et al. Intravitreal bevacizumab (Avastin) for retinal angiomatous proliferation. Retina 2007;27:451– 457.
