OCULAR ISCHEMIC SYNDROME PRESENTING AS RETINAL VASCULITIS IN A PATIENT WITH MOYAMOYA SYNDROME Evangelia Papavasileiou, MD, Lucia Sobrin, MD, MPH, George N. Papaliodis, MD
Purpose: To report a case of ocular ischemic syndrome presenting as retinal vasculitis in a patient with Moyamoya syndrome. Methods: A retrospective chart review was conducted to record clinical data including fluorescein angiography, optical coherence tomography, and serologic testing. A review of the literature from 1969 to 2014 of ocular involvement in Moyamoya syndrome was performed. Results: A 51-year-old woman with long history of bilateral retinal vasculitis and refractory cystoid macular edema was eventually diagnosed with Moyamoya syndrome after sustaining a perioperative cerebrovascular accident. Moyamoya syndrome has been associated in the literature with ocular ischemic syndrome, presenting with narrowed retinal arteries, dilated veins, and midperipheral retinal hemorrhages, but retinal vasculitis with cystoid macular edema has not been reported. Conclusion: Moyamoya-related ocular ischemic syndrome can present as retinal vascular leakage and macular edema. Ophthalmologists should be cognizant that signs of the disease may be first observed in the eye before manifestations in the cerebrovascular system. RETINAL CASES & BRIEF REPORTS 9:170–172, 2015
imaging showed bilateral intraretinal cystic spaces and thickening (Figure 1). Because of her prominent headache symptoms, she had a magnetic resonance imaging of the brain, which was normal. She underwent exhaustive serologic testing, including ANA, ds-DNA, ss-DNA, ANCA, ACE, lysozyme, ESR, CRP, RPR, antiTreponemal Ab, QuantiFERON Gold, and Lyme serology, which was negative for an underlying systemic etiology. She had bilateral intravitreal preservative-free triamcinolone injections (0.1 mL of 40 mg/mL). Her macular edema resolved after injections but recurred within 2 months. She was then treated with oral prednisone 60 mg daily with no improvement. Concurrent with the treatment of her eye condition, she decided to undergo gastric bypass surgery, and several hours postoperatively, she developed a right middle cerebral artery territory cerebrovascular accident manifested by acute leftsided weakness. Magnetic resonance imaging/magnetic resonance angiography of the brain was obtained, and the patient was determined to have radiographic and clinical features consistent with Moyamoya disease. Cerebral angiogram demonstrated a near occlusion of the supraclinoid right internal carotid artery with complete occlusion of the left anterior carotid artery and multiple leptomeningeal collaterals. To treat this condition, she underwent cerebral bypass surgery (right superficial temporal artery to middle cerebral artery bypass). Her postoperative computed tomography angiogram showed the narrowed right internal carotid artery
From the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
Case Report A 51-year-old woman with a medical history of hypertension, hypothyroidism, and persistent headaches was referred for the management of bilateral retinal vasculitis and cystoid macular edema. Visual acuities were 20/100 in the right eye and 20/32 in the left eye. Anterior segment examination was normal. There was no vitreous cell. Dilated examination showed bilateral cystoid macular edema and faint perivascular exudates. Fluorescein angiography demonstrated delayed choroidal filling, bilateral petaloid macular leakage, diffuse retinal vascular staining and leakage, and optic nerve staining consistent with retinal vasculitis and secondary cystoid macular edema (Figure 1). Optical coherence tomography None of the authors have any financial/conflicting interests to disclose. Reprint requests: George N. Papaliodis, MD, Massachusetts Eye and Ear Infirmary, 243 Charles Street, 12th floor, Boston, MA 02114; e-mail: [email protected]
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Fig. 1. Early frames of fluorescein angiogram in the right (A) and left (B) eyes show patchy choroidal filling with peripapillary areas of hypofluorescence (arrows). Late frames of the angiogram in the right (C) and left (D) eyes demonstrated leakage in a petaloid pattern in the macula, staining and leakage of the retinal vessels, and staining of the optic nerve head. Optical coherence tomography images of the right (E) and left (F) eyes showed cystoid macular edema.
(Figure 2). After her neurovascular surgery, her retinal vasculitis resolved clinically, but she had persistent bilateral macular thickening with epiretinal membranes in both eyes.
Discussion To the best of our knowledge, this is the first report of retinal vasculitis and macular edema secondary to ocular ischemic syndrome (OIS) related to Moyamoya disease. Moyamoya disease is a rare chronic progressive cerebrovascular occlusive disease that is characterized by stenosis or occlusion of the bilateral internal carotid arteries, proximal cerebral, and/or the circle of Willis arteries, leading to the development of collateral vessels around the basal ganglion region as visualized by cerebral angiography. Given the documented association of OIS with carotid occlusion and the frequent occurrence of
carotid occlusion in Moyamoya disease, one might expect that patients with Moyamoya disease would be particularly susceptible to the development of ocular ischemia. Ocular involvement in Moyamoya disease is rare with very few case reports of ophthalmic manifestations. Ophthalmic examination findings associated with Moyamoya syndrome include isolated morning glory disk anomaly (4 cases), iris hypoplasia (3 cases), Peter’s anomaly (3 cases), anterior ischemic optic neuropathy (1 case), and OIS (1 case) manifesting with neovascular glaucoma, posterior segment neovascularization, chorioretinal atrophy, central retinal vein occlusion, and retinal artery occlusion.1,2 Common findings in OIS are narrowed retinal arteries, dilated veins, and midperipheral retinal hemorrhages. However, macular edema can be seen in 17% of cases and is often accompanied by hyperfluorescence of the optic disk, caused by leakage from
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
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Fig. 2. Cerebral angiogram demonstrates a near occlusion of the supraclinoid right internal carotid artery (arrows).
disk capillaries, and retinal vessel staining and leakage.8 In 85% of eyes with OIS, staining of the major retinal vessels (mostly arteries) and their branches may be observed at the late phase of the angiogram and is attributed to the increased permeability of the vessels because of endothelial cell damage related to chronic ischemia. Angiographic findings similar to those seen in our case have been reported in patients with OIS from other etiologies such as carotid artery atherosclerosis and Takayasu arteritis.8,9 In our patient, ocular ischemia was manifested primarily as retinal vascular leakage and macular edema. The lack of response of her retinal vasculitis to high-dose systemic steroids suggested that the underlying etiology was not autoimmune or inflammatory. In addition, her serologic workup for inflammation was negative. In patients who do not respond as expected to antiinflammatory therapy, the diagnosis of a primary inflammatory retinal vasculitis should be reconsidered. The Moyamoya disease was not noticed on her original magnetic resonance imaging of the brain because angiography is required to visualize the abnormal vessels. The persistent macular edema in our case despite CNS reperfusion with graft surgery could be explained by significant damage to the blood–retinal barrier and the presence of bilateral epiretinal membranes. Reperfusion surgery often does not improve visual acuity outcomes despite improving retinal circulation times. Although up to 78% of patients with OIS may have improvement in retinal circulation time and blood flow in the ipsilateral eye after superficial temporal artery– middle cerebral artery bypass, visual acuity improvement is rare.10,11 Among a group of 13 patients with
OIS who underwent superficial temporal artery–middle cerebral artery bypass, visual acuity stabilized in 23%, worsened in 77%, and improved in none at 1-year follow-up. In our patient, the macular edema persisted, but vascular sheathing on clinical examination resolved. Although Moyamoya disease is a rare condition, it is important for the ophthalmologist to be cognizant of the ocular manifestations, as it can lead to irreversible vision loss and may be a harbinger of life-threatening CNS events. Considering that signs of the disease may be first observed in the eye before they are manifested in the cerebrovascular system, the ophthalmologist has an important role in the proper diagnosis and referral for further investigations. Collaboration between the ophthalmologist, neurologist, vascular surgeon, and primary physician is essential for appropriate management of the disease. Key words: Moyamoya syndrome, ocular ischemia, retinal vasculitis, uveitis. References 1. Suzuki J, Takaku A. Cerebrovascular “Moyamoya” disease: disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20:288–299. 2. Bakri SJ, Siker D, Masaryk T, et al. Ocular malformations, Moyamoya disease, and midline cranial defects: a distinct syndrome. Am J Ophthalmol 1999;127:356–357. 3. Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–251. 4. Noda S, Hayasaka S, Setogawa T, Matsumoto S. Ocular symptoms of Moyamoya disease. Am J Ophthalmol 1987;103:812–816. 5. Barrall JL, Summers CG. Ocular ischemic syndrome in a child with Moyamoya disease and neurofibromatosis. Surv Ophthalmol 1996;40:500–504. 6. Ushimura S, Mochizuki K, Ohashi M, et al. Sudden blindness in the fourth month of pregnancy led to diagnosis of Moyamoya disease. Ophthalmologica 1993;207:169–173. 7. Takano S, Saito M, Miyasaka Y, et al. Fundus hemorrhage in patients with intracranial hemorrhage caused by cerebrovascular disease–its clinical significance [in Japanese]. No To Shinkei 1992;44:13–17. 8. Terelak-Borys B, Skonieczna K, Grabska-Liberek I. Ocular ischemic syndrome—a systematic review. Med Sci Monit 2012;18:RA138–RA144. 9. Zhou B1, Ye P, Wei S. Preliminary clinical analysis of neovascular glaucoma secondary to carotid artery disease. Clin Exp Optom 2011;94:207–211. 10. Sivalingam A, Brown GC, Magargal LE. The ocular ischemic syndrome. III. Visual prognosis and the effect of treatment. Int Ophthalmol 1991;15:15–20. 11. Standefer M, Little JR, Tomsak R, et al. Improvement in the retinal circulation after superficial temporal to middle cerebral artery bypass. Neurosurgery 1985;16:525–529.
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
Purpose: To report a case of ocular ischemic syndrome presenting as retinal vasculitis in a patient with Moyamoya syndrome. Methods: A retrospective chart review was conducted to record clinical data including fluorescein angiography, optical coherence tomography, and serologic testing. A review of the literature from 1969 to 2014 of ocular involvement in Moyamoya syndrome was performed. Results: A 51-year-old woman with long history of bilateral retinal vasculitis and refractory cystoid macular edema was eventually diagnosed with Moyamoya syndrome after sustaining a perioperative cerebrovascular accident. Moyamoya syndrome has been associated in the literature with ocular ischemic syndrome, presenting with narrowed retinal arteries, dilated veins, and midperipheral retinal hemorrhages, but retinal vasculitis with cystoid macular edema has not been reported. Conclusion: Moyamoya-related ocular ischemic syndrome can present as retinal vascular leakage and macular edema. Ophthalmologists should be cognizant that signs of the disease may be first observed in the eye before manifestations in the cerebrovascular system. RETINAL CASES & BRIEF REPORTS 9:170–172, 2015
imaging showed bilateral intraretinal cystic spaces and thickening (Figure 1). Because of her prominent headache symptoms, she had a magnetic resonance imaging of the brain, which was normal. She underwent exhaustive serologic testing, including ANA, ds-DNA, ss-DNA, ANCA, ACE, lysozyme, ESR, CRP, RPR, antiTreponemal Ab, QuantiFERON Gold, and Lyme serology, which was negative for an underlying systemic etiology. She had bilateral intravitreal preservative-free triamcinolone injections (0.1 mL of 40 mg/mL). Her macular edema resolved after injections but recurred within 2 months. She was then treated with oral prednisone 60 mg daily with no improvement. Concurrent with the treatment of her eye condition, she decided to undergo gastric bypass surgery, and several hours postoperatively, she developed a right middle cerebral artery territory cerebrovascular accident manifested by acute leftsided weakness. Magnetic resonance imaging/magnetic resonance angiography of the brain was obtained, and the patient was determined to have radiographic and clinical features consistent with Moyamoya disease. Cerebral angiogram demonstrated a near occlusion of the supraclinoid right internal carotid artery with complete occlusion of the left anterior carotid artery and multiple leptomeningeal collaterals. To treat this condition, she underwent cerebral bypass surgery (right superficial temporal artery to middle cerebral artery bypass). Her postoperative computed tomography angiogram showed the narrowed right internal carotid artery
From the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
Case Report A 51-year-old woman with a medical history of hypertension, hypothyroidism, and persistent headaches was referred for the management of bilateral retinal vasculitis and cystoid macular edema. Visual acuities were 20/100 in the right eye and 20/32 in the left eye. Anterior segment examination was normal. There was no vitreous cell. Dilated examination showed bilateral cystoid macular edema and faint perivascular exudates. Fluorescein angiography demonstrated delayed choroidal filling, bilateral petaloid macular leakage, diffuse retinal vascular staining and leakage, and optic nerve staining consistent with retinal vasculitis and secondary cystoid macular edema (Figure 1). Optical coherence tomography None of the authors have any financial/conflicting interests to disclose. Reprint requests: George N. Papaliodis, MD, Massachusetts Eye and Ear Infirmary, 243 Charles Street, 12th floor, Boston, MA 02114; e-mail: [email protected]
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Fig. 1. Early frames of fluorescein angiogram in the right (A) and left (B) eyes show patchy choroidal filling with peripapillary areas of hypofluorescence (arrows). Late frames of the angiogram in the right (C) and left (D) eyes demonstrated leakage in a petaloid pattern in the macula, staining and leakage of the retinal vessels, and staining of the optic nerve head. Optical coherence tomography images of the right (E) and left (F) eyes showed cystoid macular edema.
(Figure 2). After her neurovascular surgery, her retinal vasculitis resolved clinically, but she had persistent bilateral macular thickening with epiretinal membranes in both eyes.
Discussion To the best of our knowledge, this is the first report of retinal vasculitis and macular edema secondary to ocular ischemic syndrome (OIS) related to Moyamoya disease. Moyamoya disease is a rare chronic progressive cerebrovascular occlusive disease that is characterized by stenosis or occlusion of the bilateral internal carotid arteries, proximal cerebral, and/or the circle of Willis arteries, leading to the development of collateral vessels around the basal ganglion region as visualized by cerebral angiography. Given the documented association of OIS with carotid occlusion and the frequent occurrence of
carotid occlusion in Moyamoya disease, one might expect that patients with Moyamoya disease would be particularly susceptible to the development of ocular ischemia. Ocular involvement in Moyamoya disease is rare with very few case reports of ophthalmic manifestations. Ophthalmic examination findings associated with Moyamoya syndrome include isolated morning glory disk anomaly (4 cases), iris hypoplasia (3 cases), Peter’s anomaly (3 cases), anterior ischemic optic neuropathy (1 case), and OIS (1 case) manifesting with neovascular glaucoma, posterior segment neovascularization, chorioretinal atrophy, central retinal vein occlusion, and retinal artery occlusion.1,2 Common findings in OIS are narrowed retinal arteries, dilated veins, and midperipheral retinal hemorrhages. However, macular edema can be seen in 17% of cases and is often accompanied by hyperfluorescence of the optic disk, caused by leakage from
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
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Fig. 2. Cerebral angiogram demonstrates a near occlusion of the supraclinoid right internal carotid artery (arrows).
disk capillaries, and retinal vessel staining and leakage.8 In 85% of eyes with OIS, staining of the major retinal vessels (mostly arteries) and their branches may be observed at the late phase of the angiogram and is attributed to the increased permeability of the vessels because of endothelial cell damage related to chronic ischemia. Angiographic findings similar to those seen in our case have been reported in patients with OIS from other etiologies such as carotid artery atherosclerosis and Takayasu arteritis.8,9 In our patient, ocular ischemia was manifested primarily as retinal vascular leakage and macular edema. The lack of response of her retinal vasculitis to high-dose systemic steroids suggested that the underlying etiology was not autoimmune or inflammatory. In addition, her serologic workup for inflammation was negative. In patients who do not respond as expected to antiinflammatory therapy, the diagnosis of a primary inflammatory retinal vasculitis should be reconsidered. The Moyamoya disease was not noticed on her original magnetic resonance imaging of the brain because angiography is required to visualize the abnormal vessels. The persistent macular edema in our case despite CNS reperfusion with graft surgery could be explained by significant damage to the blood–retinal barrier and the presence of bilateral epiretinal membranes. Reperfusion surgery often does not improve visual acuity outcomes despite improving retinal circulation times. Although up to 78% of patients with OIS may have improvement in retinal circulation time and blood flow in the ipsilateral eye after superficial temporal artery– middle cerebral artery bypass, visual acuity improvement is rare.10,11 Among a group of 13 patients with
OIS who underwent superficial temporal artery–middle cerebral artery bypass, visual acuity stabilized in 23%, worsened in 77%, and improved in none at 1-year follow-up. In our patient, the macular edema persisted, but vascular sheathing on clinical examination resolved. Although Moyamoya disease is a rare condition, it is important for the ophthalmologist to be cognizant of the ocular manifestations, as it can lead to irreversible vision loss and may be a harbinger of life-threatening CNS events. Considering that signs of the disease may be first observed in the eye before they are manifested in the cerebrovascular system, the ophthalmologist has an important role in the proper diagnosis and referral for further investigations. Collaboration between the ophthalmologist, neurologist, vascular surgeon, and primary physician is essential for appropriate management of the disease. Key words: Moyamoya syndrome, ocular ischemia, retinal vasculitis, uveitis. References 1. Suzuki J, Takaku A. Cerebrovascular “Moyamoya” disease: disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20:288–299. 2. Bakri SJ, Siker D, Masaryk T, et al. Ocular malformations, Moyamoya disease, and midline cranial defects: a distinct syndrome. Am J Ophthalmol 1999;127:356–357. 3. Brown GC, Magargal LE. The ocular ischemic syndrome. Clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11:239–251. 4. Noda S, Hayasaka S, Setogawa T, Matsumoto S. Ocular symptoms of Moyamoya disease. Am J Ophthalmol 1987;103:812–816. 5. Barrall JL, Summers CG. Ocular ischemic syndrome in a child with Moyamoya disease and neurofibromatosis. Surv Ophthalmol 1996;40:500–504. 6. Ushimura S, Mochizuki K, Ohashi M, et al. Sudden blindness in the fourth month of pregnancy led to diagnosis of Moyamoya disease. Ophthalmologica 1993;207:169–173. 7. Takano S, Saito M, Miyasaka Y, et al. Fundus hemorrhage in patients with intracranial hemorrhage caused by cerebrovascular disease–its clinical significance [in Japanese]. No To Shinkei 1992;44:13–17. 8. Terelak-Borys B, Skonieczna K, Grabska-Liberek I. Ocular ischemic syndrome—a systematic review. Med Sci Monit 2012;18:RA138–RA144. 9. Zhou B1, Ye P, Wei S. Preliminary clinical analysis of neovascular glaucoma secondary to carotid artery disease. Clin Exp Optom 2011;94:207–211. 10. Sivalingam A, Brown GC, Magargal LE. The ocular ischemic syndrome. III. Visual prognosis and the effect of treatment. Int Ophthalmol 1991;15:15–20. 11. Standefer M, Little JR, Tomsak R, et al. Improvement in the retinal circulation after superficial temporal to middle cerebral artery bypass. Neurosurgery 1985;16:525–529.
Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
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