Ophthalmic Artery Ischemic Syndrome Associated with Neurofibromatosis

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and function in patients with genetically confirmed SCA1. Report of a Case. A 3-month-old girl with neurofibro- Our data suggest that ATXN1 should be screened in all matosis type 1 was diagnosed as having moyamoya syn- patients with SCA and decreasing vision. The findings drome when she exhibited seizures and, on cerebral an- extend the range of ophthalmologic phenotypes and pro- giography, demonstrated right internal carotid artery and vide important information to assist the management of middle cerebral artery stenosis with collateral vascular- families in whom SCA1 is suspected. ization. Brain magnetic resonance imaging revealed severe right-sided hemiatrophy with laminar necrosis in the Veronika Vaclavik, MD right parietal, occipital, and temporal lobes, indicative François-Xavier Borruat, MD of a prior ischemic event (Figure 1A). A magnetic reso- Aude Ambresin, MD nance angiogram revealed an attenuated right internal Francis L. Munier, MD carotid artery, severely attenuated right cerebral arter- Author Affiliations: Department of Ophthalmology, Hoˆpi- ies, and a small right ophthalmic artery with dimin- taux Universitaires, Geneva (Dr Vaclavik), and Jules- ished flow (Figure 1B). Gonin Eye Hospital, University of Lausanne, Lausanne At age 4 months, the patient was able to fix and fol- (Drs Vaclavik, Borruat, Ambresin, and Munier), Swit- low in both eyes and exhibited no strabismus. The optic zerland. nerve and retinal examination findings were normal. At Correspondence: Dr Munier, Jules-Gonin Eye Hospi- age 6 months, she underwent a pial synangiosis, a cere- tal, Avenue de France 15, 1004 Lausanne, Switzerland bral revascularization procedure in which a donor scalp ([email protected]). artery is sutured to the surface of the brain. Author Contributions: Drs Vaclavik and Borruat con- Ophthalmic examination at age 12 months revealed tributed equally to the work and share first authorship. a preference for the left eye and a right exotropia. A Conflict of Interest Disclosures: None reported. relative afferent pupillary defect was present in the Funding/Support: This work was supported by grant right eye. Slitlamp examination findings were normal 320030-127558 from the Swiss National Science Foun- bilaterally. dation (Dr Munier). Dilated funduscopic examination of the right eye re- Previous Presentation: This paper was presented at the vealed a clear vitreous, pale optic nerve, attenuated reti- Atlantic Coast Fan Club Meeting; January 20, 2012; nal vessels with abrupt termination of the vessels, and New York, New York; and the Socie´te´ Française diffuse chorioretinal atrophy nasal to the optic nerve d’Oculogeńe´tique Francophone Annual Meeting; De- (Figure 2A). Dilated examination of the left eye showed cember 2-3, 2011; Lausanne, Switzerland. a normal retina, choroid, and optic nerve. Fluorescein angiography of the right eye demonstrated loss of reti- 1. Taroni F, DiDonato S. Pathways to motor incoordination: the inherited ataxias. nal pigment epithelium and atrophy of the choroidal vas- Nat Rev Neurosci. 2004;5(8):641-655. culature nasal to the optic nerve, with attenuated retinal 2. Pula JH, Gomez CM, Kattah JC. Ophthalmologic features of the common spinocerebellar ataxias. Curr Opin Ophthalmol. 2010;21(6):447-453. vessels (Figure 2B). Findings on fluorescein angiogra- 3. Scho¨ls L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cer- phy of the left eye were normal. ebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3(5):291-304. Brain magnetic resonance angiography at age 12 4. Rivaud-Pechoux S, Du¨rr A, Gaymard B, et al. Eye movement abnormalities months revealed increased stenosis of the right intracra- correlate with genotype in autosomal dominant cerebellar ataxia type I. Ann nial internal carotid artery and nonvisualization of the Neurol. 1998;43(3):297-302. 5. Abe T, Abe K, Aoki M, Itoyama Y, Tamai M. Ocular changes in patients with right ophthalmic artery. spinocerebellar degeneration and repeated trinucleotide expansion of spinocerebellar ataxia type 1 gene. Arch Ophthalmol. 1997;115(2):231-236. Comment. Moyamoya syndrome predisposes patients to 6. Thurtell MJ, Biousse V, Newman NJ. Rod-cone dystrophy in spinocerebellar ataxia type 1. Arch Ophthalmol. 2011;129(7):956-958. cerebrovascular ischemia as the result of stenosis of the in- 7. Garden GA, La Spada AR. Molecular pathogenesis and cellular pathology of tracranial portion of the internal carotid arteries and their spinocerebellar ataxia type 7 neurodegeneration. Cerebellum. 2008;7(2): 1 138-149. proximal branches. The development of collateral circu- 8. Birch DG, Wen Y, Locke K, Hood DC. Rod sensitivity, cone sensitivity, and lation to compensate for the cerebral ischemia produces photoreceptor layer thickness in retinal degenerative diseases. Invest Oph- an image on cerebral angiography that has been described thalmol Vis Sci. 2011;52(10):7141-7147. 9. Duenãs AM, Goold R, Giunti P. Molecular pathogenesis of spinocerebellar as a “puff of smoke,” or “moyamoya” in Japanese. ataxias. Brain. 2006;129(pt 6):1357-1370. The pathogenesis of the condition is currently un- 10. Siegert S, Cabuy E, Scherf BG, et al. Transcriptional code and disease map known, but a polygenic or autosomal dominant trans- for adult retinal cell types. Nat Neurosci. 2012;15(3):487-495, S1-S2. mission with incomplete penetrance has been sug- gested. The condition has been associated with several disorders, including neurofibromatosis type 1, sickle cell Ophthalmic Artery Ischemic Syndrome disease, and Down syndrome. Associated With Neurofibromatosis Ophthalmic examination findings associated with and Moyamoya Syndrome moyamoya syndrome include isolated morning glory disc anomaly; a syndrome consisting of morning glory disc e describe a 12-month-old girl with anomaly, optic nerve hypoplasia, chorioretinal coloboma, moyamoya syndrome and neurofibroma- sphenopharyngeal meningoencephalocele, and midline W tosis type 1 who developed profound, uni- cranial defects2; anterior ischemic optic neuropathy3; ocular lateral, ophthalmic artery ischemia. The association of ischemic syndrome, manifesting with neovascularization moyamoya syndrome with ophthalmic artery ischemia of the optic disc, venous dilation and beading, neovascu- is discussed. larization of the retina vessels, and vitreous hemorrhage4;

JAMA OPHTHALMOL/ VOL 131 (NO. 4), APR 2013 WWW.JAMAOPHTH.COM 538

MCA MCA

ICA ICA

Vertebral arteries

Figure 1. Magnetic resonance image and magnetic resonance angiogram. A, Magnetic resonance image of the brain showing severe right-sided hemiatrophy with areas of laminar necrosis in the right frontal (arrow), parietal, occipital, and temporal lobes, indicative of a prior ischemic event. The cerebral ventricles are enlarged due to cerebral atrophy (arrowhead). B, Three-dimensional, time-of flight magnetic resonance angiogram revealing a moderately attenuated right internal carotid artery (ICA) (arrowhead) and severely attenuated right middle (arrow), posterior, and bilateral anterior cerebral arteries. MCA indicates middle cerebral artery.

occurred subsequent to this cerebral ischemic event. A To our knowledge, this is the first description of a patient with evidence of retinal and choroidal infarc- tion, and consequent necrosis, from ophthalmic artery ischemia associated with moyamoya syndrome and neurofibromatosis type 1. Counseling the patient and family regarding the possibility of development of con- tralateral disease was performed and close follow-up with neurology and neurosurgery was recommended. Matthew T. Witmer, MD Richard Levy, MD B Kaleb Yohay, MD Szilard Kiss, MD Published Online: February 21, 2013. doi:10.1001 /jamaophthalmol.2013.2902 Author Affiliations: Departments of Ophthalmology (Drs Witmer, Levy, and Kiss) and Neurology (Dr Yohay), Weill Cornell Medical College, New York, New York. Correspondence: Dr Witmer, Department of Ophthal- mology, Weill Cornell Medical College, 1305 York Ave, 11th Floor, New York, NY 10021 ([email protected] .edu). Figure 2. Retcam (Clarity Medical Systems, Inc) color photograph and Conflict of Interest Disclosures: None reported. fluorescein angiogram. A, Retcam color photograph of the right eye showing Funding/Support: This work was supported by a depart- a pale optic nerve (arrowhead), attenuated retinal arcade vessels, and severe chorioretinal scarring nasal to the optic nerve (arrow). B, Retcam fluorescein mental grant from Research to Prevent Blindness. angiogram of the right eye at 1 minute demonstrating attenuation of the 1. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl retinal vessels (arrowhead) as well as atrophy of the retinal pigment JMed. 2009;360(12):1226-1237. epithelium and choroidal (arrow) vasculature nasal to the optic nerve. 2. Bakri SJ, Siker D, Masaryk T, Luciano MG, Traboulsi EI. Ocular malforma- tions, moyamoya disease, and midline cranial defects: a distinct syndrome. central retinal vein occlusion5; and central retinal artery Am J Ophthalmol. 1999;127(3):356-357. 6 3. Chen CS, Lee AW, Kelman S, Wityk R. Anterior ischemic optic neuropathy occlusion. in moyamoya disease: a first case report. Eur J Neurol. 2007;14(7):823-825. Our patient demonstrated severe optic nerve, reti- 4. Barrall JL, Summers CG. Ocular ischemic syndrome in a child with moyamoya disease and neurofibromatosis. Surv Ophthalmol. 1996;40(6):500-504. nal, and choroidal ischemia, indicative of an ophthal- 5. Slamovits TL, Klingele TG, Burde RM, Gado MH. Moyamoya disease with cen- mic artery occlusion at age 1 year. The patient showed tral retinal vein occlusion: case report. J Clin Neuroophthalmol. 1981;1(2): evidence of a prior unilateral stroke but had normal 123-127. 6. Ushimura S, Mochizuki K, Ohashi M, Ito S, Hosokawa H. Sudden blindness findings on retinal and optic nerve examination at age in the fourth month of pregnancy led to diagnosis of moyamoya disease. 4 months. We believe that the ocular ischemia Ophthalmologica. 1993;207(4):169-173.

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