Journal of Neuro-Ophthalmology:
Ocular Ischemic Syndrome Secondary to Carotid Artery Occlusion as a Late Complication of Radiotherapy of Nasopharyngeal Carcinoma
Tang, Yamei MD, PhD; Luo, Donghua MD; Peng, Wei MD; Huang, Fengting MD; Peng, Ying MD, PhD
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: firstname.lastname@example.org
A 39-year-old Chinese man developed ocular ischemic syndrome (OIS) in both eyes 14 years after radiation therapy for nasopharyngeal squamous cell carcinoma. Digital subtraction angiography disclosed occlusion of common carotid arteries and stenosis of both vertebral arteries. Following stenting of the vertebral arteries, visual function improved and ophthalmoscopic abnormalities of OIS regressed in the right eye. Radiation therapy of the head and neck has a relatively high likelihood of causing vascular stenosis. However, we believe this to be the first reported case of OIS following radiotherapy for nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is highly prevalent in south China, especially in Guangdong province. Radiotherapy has been an effective treatment for this disease, but there are many potential complications, including temporal lobe necrosis, cranial nerve injury, cognitive impairment (1), and severe skin damage (2).
Radiotherapy also induces large artery stenosis or occlusion (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 vertebral arteries induced by radiotherapy for NPC.
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 additional 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 nonreactive. 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 fluorescein 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 recurrence, and no evidence of metastasis was found. Blood pressure in both arms was 120/80 mm Hg, with no difference 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, antinuclear antigen, anti-double stranded DNA, and antiphospholipid antibodies were normal.
Brain CT was normal. Duplex ultrasound of the carotid arteries displayed occlusion of both CCAs. Digital subtraction 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 performed 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 transient visual loss resolved in 1 month, and dizziness disappeared 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 abnormalities 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.
Radiotherapy is an important treatment modality for patients with head and neck cancer. With improved patient survival, attention has focused on radiation-induced deficits (6). One such complication is carotid artery stenosis 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 previously (mean 79.9 months) and 96 healthy individuals as controls. Using color-flow duplex ultrasonography, these investigators found 18 patients (16%) had marked stenosis (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 stenosis (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.
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 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.
11. Lam WW,
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.
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