| OCR Text |
Show Ocular Ischemic Syndrome Secondary to Carotid Artery Occlusion as a Late Complication of Radiotherapy of Nasopharyngeal Carcinoma Yamei Tang, MD, PhD, Donghua Luo, MD, Wei Peng, MD, Fengting Huang, MD, Ying Peng, MD, PhD Abstract: A 39-year-old Chinese man developed ocular ischemic syndrome (OIS) in both eyes 14 years after radiation therapy for nasopharyngeal squamous cell car-cinoma. Digital subtraction angiography disclosed oc-clusion of common carotid arteries and stenosis of both vertebral arteries. Following stenting of the vertebral ar-teries, visual function improved and ophthalmoscopic abnormalities of OIS regressed in the right eye. Radiation therapy of the head and neck has a relatively high likeli-hood of causing vascular stenosis. However, we believe this to be the first reported case of OIS following radio-therapy for nasopharyngeal carcinoma. Journal of Neuro-Ophthalmology 2010;30:315-320 doi: 10.1097/WNO.0b013e3181dee914 2010 by North American Neuro-Ophthalmology Society Nasopharyngeal carcinoma (NPC) is highly prevalent in south China, especially in Guangdong province. Radiotherapy has been an effective treatment for this dis-ease, but there are many potential complications, including temporal lobe necrosis, cranial nerve injury, cognitive im-pairment (1), and severe skin damage (2). Radiotherapy also induces large artery stenosis or oc-clusion (3-5), which may lead to hypoperfusion of the ophthalmic artery and the ocular ischemic syndrome (OIS). We describe a case of OIS secondary to occlusion of the common carotid arteries (CCAs) and stenosis of the ver-tebral arteries induced by radiotherapy for NPC. CASE REPORT A 39-year-old Chinese man was admitted to our hospital complaining of blurred vision, transient blindness of both eyes, and dizziness. Fourteen years earlier, he had been diagnosed as having stage T1N1M0 squamous NPC. He had received external radiation therapy to the nasopharynx with a total dose of 72 Gy in 36 fractions over 74 days and a supplemental dose of 59.42 Gy to the neck in 33 addi-tional fractions. He had remained clinically stable over the next 14 years. Our examination disclosed best-corrected visual acuities of 20/40 in the right eye and 20/400 in the left eye. The right pupil measured 4 mm and reacted minimally to direct light, and the left pupil measured 7 mm and was non-reactive. Intraocular pressures were 12 mm Hg in the right eye and 8 mm Hg in the left eye. The anterior ocular segments were normal, and visual field testing showed nasal field loss in each eye (Fig. 1). Ophthalmoscopy and fluo-rescein angiography revealed narrowed retinal arterioles, retinal vascular changes including microaneurysms, and delayed arm-to-retina circulation time on the right (Fig. 2). There were no other neurological deficits. Endoscopic examination of the nasopharynx did not reveal tumor re-currence, and no evidence of metastasis was found. Blood pressure in both arms was 120/80 mm Hg, with no dif-ference detected during sitting and lying down. No carotid bruits were noted. Complete blood count, erythrocyte sedimentation rate, C-reactive protein, fasting blood sugar, lipid profile, anti-nuclear antigen, anti-double stranded DNA, and anti-phospholipid antibodies were normal. Departments of Neurology (YT, YP), Ophthalmology (WP), and Internal Medicine (FH), The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; and Department of Nasopharyngeal Carcinoma (DL), Cancer Center of Sun Yat-sen University, Guangzhou, China. Supported by the Chinese government through the National Natural Science Foundation of China (NSFC 30600164) and by the Second Affiliated Hospital of Sun Yat-Sen University through Yat-Sen Scholarship for Young Scientist. Address correspondence to Yamei Tang, MD, PhD, Department of Neurology, The Second Affiliated Hospital, Sun Yat-Sen University, Number 102, Yan Jiang Xi Road, Guangzhou, Guangdong Province, China; E-mail: yameitang@hotmail.com. Tang et al: J Neuro-Ophthalmol 2010; 30: 315-320 315 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Brain CT was normal. Duplex ultrasound of the carotid arteries displayed occlusion of both CCAs. Digital subtrac-tion cervicocerebral angiography revealed occlusion of the long segment of both CCAs and stenosis of both vertebral arteries at their origins (Fig. 3). Endovascular stenting of the vertebral arteries was per-formed first on the left side and then on the right side with an interval of 3 months. After the stenting, the patient was treated with antiplatelet therapy. Blurred vision and tran-sient visual loss resolved in 1 month, and dizziness dis-appeared 3 months later. Reassessment digital subtraction angiography revealed filling of both vertebral arteries at the site of previous stenosis (Fig. 3). Six months after stenting, the retinal vascular abnor-malities had improved (Fig. 4), visual acuity in the right eye was 20/30, and the visual field had improved (Fig. 5). However, the left eye developed a vitreous hemorrhage and a cataract 4 months after stenting. DISCUSSION Radiotherapy is an important treatment modality for patients with head and neck cancer. With improved pa-tient survival, attention has focused on radiation-induced deficits (6). One such complication is carotid artery ste-nosis following radiation for NPC (3, 4, 7-18) (Table 1). Cheng et al (10) studied 96 patients who had undergone cervical radiotherapy for NPC at least 12 months pre-viously (mean 79.9 months) and 96 healthy individuals as controls. Using color-flow duplex ultrasonography, these investigators found 18 patients (16%) had marked stenosis FIG. 1. Visual fields before stenting. Nerve fiber bundle defects are evident in both eyes. Mean deviations are 210.17 dB in the right eye and 27.36 dB in the left eye. FIG. 2. Fundus photography and fluorescein angiography before stenting. Fundus photographs of the right eye (A) and left eye (B) show narrowed arterioles (black arrows) and microaneurysms and abnormal arterial communications (blue arrows). Fluorescein angiography of the right eye at 2 minutes 53 seconds (C) shows retinal venous and choroidal flush (black arrows), suggesting prolonged arm-to-retina circulation time. Fluorescein angiography of the left eye (D) at 1 minute 3 seconds already shows retinal venous and choroidal flush, suggesting normal circulation time. Original Contribution 316 Tang et al: J Neuro-Ophthalmol 2010; 30: 315-320 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. (70%-99%) and 35 (37%) had moderate stenosis (30%- 69%) of either the common carotid or internal carotid artery. Four of the former vessels and 6 of the latter were totally occluded at the time of examination. In the control group 8 patients (8%) were found to have moderate ste-nosis (30%-69%) and none had marked stenosis or total occlusion. Multivariate logistic regression analysis found that smoking, post-radiotherapy interval, cerebrovascular symptoms, and absence of head and neck surgery were independent predictive factors of severe common carotid artery/internal carotid artery stenosis following radiation therapy. The development of carotid stenosis as well as vertebral artery stenosis following radiotherapy for NPC was confirmed by Lam and co-workers (12), although hypercholesterolemia, hyperglycemia and smoking were not found to be independent risk factors. In a follow-up study, Cheng et al (16) reported an annualized progression rate from less than 50% stenosis to 50% or greater stenosis in 15.4% of irradiated arteries compared to 4.8% in non-irradiated arteries. A number of mechanisms may lead to this vascular complication (12, 19). These include damage or occlusion of the vasa vasorum causing ischemic necrosis of the vessel wall, creation of adventitial fibrosis leading to vascular obstruction, and acceleration of atherosclerosis. Our patient developed OIS due to impaired flow of multiple vessels of the cerebrovascular system. It appears advisable that regular diagnostic follow-up studies of the carotid and vertebral systems be undertaken in patients following radiotherapy for NPC until treatment guidelines are developed based on longterm observational studies. As in our patient, stenting of the vertebral and carotid systems may offer a successful form of therapy in selected cases. REFERENCES 1. Welzel G, Fleckenstein K, Mai SK, Hermann B, Kraus- Tiefenbacher U, Wenz F. Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors. Strahlenther Onkol. 2008;184:647-654. 2. Bolke E, Gerber PA, Lammering G, Peiper M,Muller-Homey A, Pape H, Giro C, Matuschek C, Bruch-Gerharz D, Hoffmann TK, Gripp S, Homey B, Budach W. Development and FIG. 3. Carotid angiogram before and after bilateral vertebral artery stenting. A. Long segmental occlusion of both common carotid arteries is evident (dashed lines), and there is stenosis of left vertebral artery at its origin (arrow). B. After stenting, the left vertebral artery stenosis has been corrected (arrow). C. Magnified view of stenosis of the right vertebral artery (arrow) before stenting. D. After stenting, the right vertebral artery stenosis has been corrected (arrow). Original Contribution Tang et al: J Neuro-Ophthalmol 2010; 30: 315-320 317 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. TABLE 1. Reported cases of carotid artery stenosis secondary to radiotherapy for nasopharyngeal and other head and neck cancers Authors Year No. of Patients Age (y) Radiation Dosage (Gy) Postradiotherapy Interval (y) Malignancy Site Radiation Area Symptoms Carotid Artery Status Horimoto et al (7) 1996 1 56 120 5 Pharyngeal cancer Bilateral cervical fields TIA, stroke Occlusion of right ICA and stenosis of left ICA Nishi et al (8) 1997 1 60 50 15 Cancer in left neck Left neck Not documented Left CAS Dubec et al (9) 1998 45 67 (43-90) 35-62 .5 Head and neck cancers Not documented Not documented 85% patients have CAS Cheng et al (10) 2000 96 53.6 (25-77) 45-72 6.6 6 5.3 Nasopharyngeal cancer Primary site and neck Cerebral vascular disease Severe CAS Lam et al (11) 2001 24 53 (38-69) 56.6 4-26 Nasopharyngeal cancer Primary site and neck TIA, stroke Stenosis in the ECA in 24 patients Lam et al (12) 2001 71 53.6 (38-64) 56.4 4-20 Nasopharyngeal cancer Primary site and neck Cerebral vascular disease Severe CAS Koenigsberg et al (13) 2001 1 72 60-72 13 Laryngeal cancer Not documented TIA, neck pain Bilateral CAS, common carotid pseudoaneurysms Kang et al (14) 2002 12 60 (21-84) 50.4-70.2 8.5 (2-30) Head and neck cancers Primary site and neck TIA, stroke Stenosis of CCA and ICA in 7 patients Steele et al (15) 2004 40 68.2 (26-87) 64 10.2 Head and neck cancers Not documented Stroke Unilateral carotid artery occlusion in 15% patients, bilateral CAS in 15% patients Cheng et al (16) 2004 95 60 6 15 (19-86) 120 7.6 6 6.4 Head and neck cancers Bilateral cervical fields Not documented High stenosis progression rate Avitia et al (3) 2006 1 73 54-70 18 Right auricle cancer and cervical metastases Primary site and neck Stroke 70%-80% stenosis of the right ICA, occlusion 3 years later Liao et al (17) 2007 1 47 70.8 9 Nasopharyngeal cancer Bilateral cervical fields TIA 80% stenosis of the left ICA Leung et al (18) 2007 1 57 Not documented 30 Nasopharyngeal cancer Not documented Poor short-term memory Stenosis of bilateral CCA and ICA Favre et al (4) 2008 135 67 6 8 (43-88) Not available 12 6 8 Not available Not available Not available Mean diameter reduction of carotid artery 81% CAS, carotid artery stenosis; CCA, common carotid artery; ECA, external carotid artery; ICA, internal carotid artery; TIA, transient ischemic attack. Original Contribution 318 Tang et al: J Neuro-Ophthalmol 2010; 30: 315-320 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. management of severe cutaneous side effects in head-and-neck cancer patients during concurrent radiotherapy and cetuximab. Strahlenther Onkol. 2008;184:105-110. 3. Avitia S, Hamilton J, Osborne RF. Radiation-induced carotid artery stenosis. Ear Nose Throat J. 2006;85:158. 4. Favre JP, Nourissat A, Duprey A, Nourissat G, Albertini JN, Becquemin JP. Endovascular treatment for carotid artery stenosis after neck irradiation. J Vasc Surg. 2008;48: 852-858. 5. Tacconi S, Bieri S. Renal artery stenosis after radiotherapy for Ewing's sarcoma. Strahlenther Onkol. 2008;184:478-483. 6. Tang Y, Zhang Y, Guo L, Peng Y, Luo Q, Xing Y. Relationship between individual radiosensitivity and radiation encephalopathy of nasopharyngeal carcinoma after radiotherapy. Strahlenther Onkol. 2008;184:510-514. 7. Horimoto M, Kodama N, Takamatsu H. Bilateral internal carotid artery disease secondary to cervical radiation. A case report. Angiology. 1996;47:609-613. 8. Nishi K, Uno M, Ueda S, Nishitani K, Shinno K, Nagahiro S, Horiguchi H, Sano T. Carotid endarterectomy for radiation-induced carotid artery stenosis. Neurol Med Chir (Tokyo). 1997;37:844-848. 9. Dubec JJ, Munk PL, Tsang V, Lee MJ, Janzen DL, Buckley J, Seal M, Taylor D. Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy. Br J Radiol. 1998;71:872-875. 10. Cheng SW, Ting AC, Lam LK, Wei WI. Carotid stenosis after radiotherapy for nasopharyngeal carcinoma. Arch Otolaryngol Head Neck Surg. 2000;126:517-521. FIG. 4. Fundus photography of retinal vasculature of right eye before and 6 months after bilateral vertebral artery stenting. Before stenting (left), narrowed retinal arterioles and microaneurysms (blue arrows) and poor vascular anastomoses (black arrows) are evident, as shown in Figure 1. After stenting (right), these abnormalities are less evident. FIG. 5. Visual field of right eye 6 months after bilateral vertebral artery stenting. The defect is less prominent than preoperatively (Fig. 1), and the mean deviation has lessened from 210.17 dB to 24.16 dB. Original Contribution Tang et al: J Neuro-Ophthalmol 2010; 30: 315-320 319 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 11. LamWW, Yuen HY, Wong KS, Leung SF, Liu KH, Metreweli C. Clinically underdetected asymptomatic and symptomatic carotid stenosis as a late complication of radiotherapy in Chinese nasopharyngeal carcinoma patients. Head Neck. 2001;23:780-784. 12. Lam WW, Leung SF, So NM, Wong KS, Liu KH, Ku PK, Yuen HY, Metreweli C. Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer. 2001;92:2357-2363. 13. Koenigsberg RA, Grandinetti LM, Freeman LP,McCormick D, Tsai F. Endovascular repair of radiation-induced bilateral common carotid artery stenosis and pseudoaneurysms: a case report. Surg Neurol. 2001;55:347-352. 14. Kang JH, Kwon SU, Kim JS. Radiation-induced angiopathy in acute stroke patients. J Stroke Cerebrovasc Dis. 2002;11: 315-319. 15. Steele SR,Martin MJ,Mullenix PS, Crawford JV, Cuadrado DS, Andersen CA. Focused high-risk population screening for carotid arterial stenosis after radiation therapy for head and neck cancer. Am J Surg. 2004;187:594-598. 16. Cheng SW, Ting AC, Ho P, Wu LL. Accelerated progression of carotid stenosis in patients with previous external neck irradiation. J Vasc Surg. 2004;39:409-415. 17. Liao WW, Yeh YL, Wang KC, Chang Y. Postoperative transient ischemic attack in a patient with radiation-induced internal carotid artery stenosis. J Clin Anesth. 2008;20:72-73. 18. Leung GK, Chan SK, Hung KN. Triology of neurosurgical complications after radiotherapy for nasopharyngeal carcinoma. Surg Neurol. 2007;68:466-470. 19. Abayomi OK. Neck irradiation, carotid injury and its consequences. Oral Oncol. 2004;40:872-878. Original Contribution 320 Tang et al: J Neuro-Ophthalmol 2010; 30: 315-320 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
