Moyamoya disease is characterized by progressive stenosis of the internal carotid arteries and secondary angiogenesis forming a network of collateral vessels. It was first described in 1957 by Takeuchi and Shimizu and named in Japanese after the characteristic “puff of smoke” appearance on angiography.1 When secondary to an associated disease, it is referred to as moyamoya syndrome.2–5 Hemoglobin Southampton was first described in 1972 by the Southampton University Hospital Group.6 It consists of a substitution error of a proline for leucine at beta 106 that distorts the hemoglobin tertiary structure and manifests as hemolytic anemia.6 As in other hemoglobinopathies, hemoglobin Southampton can rarely lead to moyamoya syndrome.3,4,7 Central retinal artery occlusion (CRAO) resulting from moyamoya disease is rare.8–11 To the best of our knowledge, herein we report the first case of CRAO occurring in moyamoya syndrome associated with hemoglobin Southampton.
A 12-year-old Hispanic girl with a history of Southampton hemoglobinopathy (from a heterozygous de novo mutation) status post-splenectomy with moyamoya syndrome awoke with painless vision loss to no light perception in her left eye (OS). In the emergency department, vision OS had recovered to hand motions. Within 1 hour, near visual acuity (VA) measured by the ophthalmologist was J1+ in the right eye (OD) and J1 OS. No afferent pupillary defect was observed, and both anterior segment and fundus examinations were unremarkable bilaterally. No emboli, retinal whitening, or hemorrhages were observed. Cranial nerves were intact bilaterally. It was concluded that the vision loss was most likely ischemic in nature, and this was consistent with a magnetic resonance angiogram (Figure 1A), which showed complete absence of flow in her left internal carotid artery and right supraclinoid internal carotid artery, and computed tomography angiography (Figure 1B), which showed occlusion of the left internal carotid artery and left ophthalmic artery.
(A) Time-of-flight magnetic resonance angiogram scan of the head in the coronal view demonstrating complete absence of flow in the left internal carotid artery (red arrow) and absence of flow in the right supraclinoid internal carotid artery (green arrow). (B) Axial computed tomography angiography of the head demonstrating occlusion of the left cavernous internal carotid artery (red arrow).
Seven months after her visual symptoms began, VAs were 20/20 OD and 20/20-1 OS. Amsler grid testing showed a superior paracentral scotoma in her left eye. There were no emboli or retinal whitening on funduscopic exam, but narrowing of retinal vessels was noted OS (Figure 2A). Ultra-widefield fluorescein angiography (UWF-FA) had normal filling times OS and complete retinal vascular filling without collateralization (Figure 2B). Spectral-domain optical coherence tomography (SD-OCT) revealed diffuse inner retinal thinning greatest along the inferotemporal arcade (Figures 3A and 3B). Outer retinal and choroidal thickness and architecture appeared intact. OCT angiography (OCTA) demonstrated preservation of both superficial and deep vascular plexuses, although artefactual displacement of vascular layers was observed due to errors in automated segmentation (Figures 3C and 3D). The patient was diagnosed with reperfused CRAO OS. Planned definitive management includes unrelated donor allogeneic stem cell transplantation for her hemoglobinopathy and central nervous system revascularization surgery to prevent worsening moyamoya syndrome and future cerebrovascular accidents. Visual field testing performed 9 months after visual symptoms began was unremarkable OD but revealed residual defects in the inferior visual field OS, suggesting ongoing vascular insult.
(A) Color fundus photography at 7 months after central retinal artery occlusion demonstrating no residual retinal whitening, hemorrhages, emboli, collaterals, or retinal neovascularization present in both eyes. Narrowing of retinal vessels in the left eye (OS). (B) Ultra-widefield fluorescein angiography at 7-months follow-up demonstrating normal filling times and complete retinal vascular filling without collateralization OS.
Spectral-domain optical coherence tomography (OCT) retinal thickness maps of the right (A) and left (B) maculas at 7-months follow-up revealing diffuse retinal thinning temporally in both eyes greatest along the inferotemporal arcade in the left eye (OS). OCT angiography at 7-months follow-up of (C) superficial and (D) deep vascular plexus demonstrating preservation of both superficial and deep vascular plexuses within the macula OS. There is arcuate pattern of artefactual absence of superficial vascular plexus inferior to the fovea that is captured in the deep vascular plexus images of the same region.
The incidence of moyamoya in the United States is low (estimated at 0.086/100,000 persons in one of the largest moyamoya cohorts from the western United States), particularly among Hispanics.12 There is a bimodal peak incidence of moyamoya with the first and tallest peak occurring around 5 years of age and the smaller second peak incidence occurring between 30 years to 50 years of age.13 Moyamoya syndrome presents most commonly in pediatric patients as ischemic events. Hemorrhagic events are rare and represent less than 3% of presenting symptoms.14 Symptomatic ischemic events include ischemic stroke, transient ischemic attack, migraine headaches, and seizures.13 CRAO is a possible sequela of moyamoya syndrome resulting from Southampton hemoglobinopathy that can present as amaurosis fugax in the pediatric patient population.
The pathophysiology of hemoglobinopathies leading to moyamoya syndrome has been hypothesized to be the result of increased stress on the vasculature walls, from rigid red blood cells, resulting in vessel wall ischemia and subsequent endothelial proliferation. This endothelial proliferation results in subsequent vascular occlusion.3,4 Large vessel vascular occlusion then results in compensatory angiogenesis and the classic telangiectatic network of small vessels seen in moyamoya syndrome.11 Although moyamoya classically involves the internal carotid artery near the ophthalmic artery branch point, it is hypothesized that CRAO and other retinal pathology are seen infrequently as a result of the slow progressive nature of the syndrome, allowing formation of small compensatory collateral vessels to prevent retinal ischemia.11
Although hemoglobinopathies can result in progressive retinal microvasculature occlusions and inner retinal thinning, the lack of nonperfusion on UWF-FA and OCTA or retinal thinning OD by SD-OCT confirms the mechanism of injury OS was occlusive large vessel disease, or central retinal artery occlusion. Similar to other hemoglobinopathies, the distribution of inner retinal thinning and subsequent visual field loss favored permanent insults to the temporal retina.15,16 SD-OCT was helpful at demonstrating areas of greater prior ischemic insult as retinal thinning but did not show inner layer hyperreflectivity of acute ischemia. UWF-FA and OCTA did not demonstrate filling voids or residual small vessel defects, small vessel remodeling, or retinal collateralization. These technologies may prove more useful during the acute episode or its convalescence.
Treatment for moyamoya syndrome involves medical therapy and surgical revascularization. Antiplatelet agents can reduce the risk of ischemic events. Calcium channel blockers have been used for the classic migraine headaches associated with moyamoya but must be used with caution, along with other drugs that may cause hypotension, as not to precipitate ischemic events.5,17 Surgical revascularization involves using the external carotid artery to perfuse areas ischemic from internal carotid artery stenosis. It can be achieved with a direct or indirect approach. In direct revascularization, most commonly the superficial temporal artery is anastomosed to the middle cerebral artery.14,17 Indirect revascularization procedures include rerouting superficial arteries to the cerebral circulation.5,17,18
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- Goodwin PL, Vaphiades MS, Johnson AP, Stroud CE. Bilateral central retinal artery occlusion associated with moyamoya syndrome in a sickle cell disease patient. Neuroophthalmology. 2008;32(1):21–26. doi:10.1080/01658100701818156 [CrossRef]
- Lad EM, Lad SP, Ung C, Jain A, Steinberg GK, Gaynon MW. Complete visual recovery after incipient CRAO due to ocular hypoperfusion in a patient with moyamoya disease. Retin Cases Brief Rep. 2013;7(3):248–251. doi:10.1097/ICB.0b013e31828eef20 [CrossRef]
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