Intravitreal bevacizumab (Avastin®) for radiation retinopathy neovascularization

Abstract

Editor, Radiation retinopathy is a potentially severe complication of radiation therapy of ocular, nasal and paranasal malignancies. It is associated with slowly progressive vasculopathy, which may lead to capillary non-perfusion, large vessel occlusion, retinal vascular incompetence, neovascularization and other sequelae (Maguire & Schachat 2001). It has been shown that the radiation dose and the area irradiated are the most important risk factors in the development of this complication (Takeda et al. 1999): retinal complications are rare if the patient receives less than 50 Gy. The interval between the treatment and the onset of retinopathy varies, generally being higher than 2 years. In this article, we report the regression of retinal neovascularization associated with radiation retinopathy following intravitreal bevacizumab injection. A 33-year-old man with an adenoid cystic carcinoma in the right maxillary sinus, T4 N0 M0, began the treatment with stereotactic radiotherapy (total dose received 66 Gy) in May 2004. He was also treated with chemotherapy 8 months later (Cisplatin, Pfizer, New York, NY, USA; Vinorelbine, Navelbine®, Pierre Fabre Laboratories, Castres, France). Twenty-nine months after radiotherapy he developed a radiation retinopathy in his right eye. Baseline best corrected visual acuity (BCVA) in the right eye was 20/100. Slit-lamp exploration showed only a moderate–severe posterior subcapsular cataract. Ophthalmoscopy revealed inferior vitreous haemorrhage, deep retinal haemorrhages around the fovea and new vessels in the superotemporal branch artery. Fluorescein angiography obtained with Heidelberg retina autograph 2 (HRA-II) showed retinal neovascularization with peripheral retinal and macular ischaemia (Fig. 1A). We decided to initiate panretinal photocoagulation without new vessels regression 3 weeks later (Fig. 1B). Intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) was then performed. Two days later, ophthalmoscopy and angiography showed no retinal neovascularization, persisting mild vitreous haemorrhage (Fig. 1C). Two months after injection, the angiography was stable, with no signs of neovascularization and less vitreous haemorrhage (Fig. 1D). Visual acuity remained 20/100. Bevacizumab in radiation retinopathy neovascularization. This composite image contains fluorescein angiographic images over time. Central opacity is the result of moderate–severe posterior subcapsular cataract. (A) Prior to any treatment, fluorescein angiogram reveals neovascularization in the superotemporal branch artery with peripheral retinal and macular ischaemia. (B) After panretinal laser photocoagulation, fluorescein angiogram showed persistent retinal neovascularization. (C) Two days after intravitreal bevacizumab injection, there is no sign of new vessels in the superotemporal branch artery. (D) Two months after the injection of bevacizumab, fluorescein angiography is stable with no retinal neovascularization. Radiation retinopathy neovascularization is an abnormal response to retinal capillary non-perfusion induced by radiation. Treatments for radiation retinopathy include panretinal laser photocoagulation (Kinyoun et al. 1996), scatter photocoagulation and hyperbaric oxygen therapy. Bevacizumab (Avastin®; Genentech Inc., San Francisco, California, USA) is a humanized recombinant antibody that binds all isoforms of vascular endothelial growth factor (VEGF), which has been closely related with retinal neovascularization pathogenesis. The Food and Drug Administration (FDA) approved its use as an antiangiogenic agent for metastatic colorectal cancer. Several studies have shown promising results using off-label intravitreal bevacizumab for the treatment of ischaemic-proliferative retinopathies such as diabetic iris and retinal neovascularization (Avery et al. 2006) and retinal neovascularization caused by sickle cell retinopathy (Siqueira et al. 2006). Panretinal laser photocoagulation has been proved to be effective in treating radiation-induced high-risk neovascularization (Kinyoun et al. 1996) but the short interval (just 2 days) between the intravitreal bevacizumab injection and the neovascularization regression in our patient led us to think that there is a cause-and-effect relationship. The retinal neovascularization disappeared just 2 days after injection. There were no systemic or ocular side effects after intravitreal bevacizumab use, which has been used safely and effectively in achieving regression of neovascularization associated to radiation retinopathy. This positive result, in a single patient with a follow-up of 2 months, suggests that larger and longer studies could be required to assess the role of intravitreal bavacizumab in the treatment of radiation retinopathy neovascularization. The authors indicate no financial support. None of the authors have a conflict of interest involving any aspect of this article. This study adhered to the tenets of the Declaration of Helsinki and all the state laws of Spain. Legally effective informed consent was obtained from the subject.