Unilateral Blindness With Bilateral Brain Infarction After Cosmetic Facial Filler Injection

To describe a case of bilateral brain infarction associated with iatrogenic ophthalmic artery occlusion after cosmetic facial filler injection and to elucidate the pathogenic mechanism of bilateral brain infarction.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Unilateral Blindness With Bilateral Brain Infarction After Cosmetic Facial Filler Injection Jong Suk Lee, MD, Jun Yup Kim, MD, Se Joon Woo, MD, PhD Background: To describe a case of bilateral brain infarction associated with iatrogenic ophthalmic artery occlusion after cosmetic facial filler injection and to elucidate the pathogenic mechanism of bilateral brain infarction. Methods: Case report and review of the literature. Results: A case of unilateral blindness due to iatrogenic ophthalmic artery occlusion accompanied by bilateral brain infarction after cosmetic facial filler injection is described. Fluorescein angiographic images demonstrate ischemia of the retina and choroid. Associated bilateral brain infarction was observed on MRI. Conclusions: Bilateral embolic events after facial filler injection are very rare. However, several cases of unilateral iatrogenic ophthalmic or retinal artery occlusion accompanied by bilateral brain infarction have been reported. The possible route of filler material to the contralateral cerebral artery is through the anterior communicating artery. Brain infarction, especially contralateral embolic events, should be considered in severe cases of iatrogenic ophthalmic artery occlusion after facial filler injection. Journal of Neuro-Ophthalmology 2021;41:e566–e571 doi: 10.1097/WNO.0000000000001009 © 2020 by North American Neuro-Ophthalmology Society O cclusion of the ophthalmic artery and/or its branches is a rare but devastating complication associated with cosmetic facial filler injection (1,2), and the exact patho- Department of Ophthalmology (JSL, SJW), Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; and Department of Neurology (JYK), Seoul National University College of Medicine, Cerebrovascular Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Supported the NRF Bio & Medical Technology Development Program (Grant No. 2018M3A9B5021319) funded by the Korean government (MSIP and MSIT). The funding organization had no role in the design or conduct of this study. JS Lee and JY Kim contributed equally to this work and should be considered equivalent authors. The authors report no conflicts of interest. Address correspondence to Se Joon Woo, MD, PhD, Department of Ophthalmology, Seoul National University Bundang Hospital, 17382 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, South Korea; E-mail: [e-mail] e566 genic mechanism of iatrogenic ophthalmic artery occlusion (IOAO) and/or its branches after facial filler injection is not clear, but retrograde spreading of embolic materials is considered the most reasonable mechanism (2). Embolic material (typically autologous fat or hyaluronic acid) that is accidentally injected into facial cutaneous arterioles fills the lumen of the involved vessel and may be pushed proximally against arterial flow with great injecting pressure (1,2). Embolic material that reaches any branching point of the ophthalmic artery is disseminated at the branching point and is delivered to the distal portion, obstructing the distal part of the ophthalmic artery and its branches. If the amount of injected filler and injection pressure are sufficient, the embolic material can be pushed to the internal carotid artery and involve any cerebral arteries (3). There have been previous reports of concomitant brain infarction and IOAO after cosmetic facial filler injections (1,4–12). However, to the best of our knowledge, very few cases of bilateral cerebral infarction after a single procedure have been reported, and no study has revealed the mechanism of bilateral embolic events. Here, we report a case of unilateral IOAO and concomitant bilateral brain infarction after hyaluronic acid (HA) filler injection. We also analyzed previously reported cases of bilateral embolic events after cosmetic facial filler injection and elucidated the pathogenic mechanism and pathway of bilateral embolic spreading. CASE REPORT A 39-year-old woman with no underlying disease presented with vision loss and ocular pain in the left eye and motor weakness of the right upper and lower limbs immediately after hyaluronic acid cosmetic facial filler (Bellast; Dongkook Pharmaceutical Co, Seoul, Republic of Korea) injection into her glabella. Her vision was 20/20 in the right eye with no light perception in the left eye. Her left pupil was dilated without light reflex. On physical examination, her vital signs were stable and there was no fever. Neurologic examination Lee et al: J Neuro-Ophthalmol 2021; 41: e566-e571 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution indicated a deep drowsy mental status with intact brainstem signs, dysarthria, right arm dominant quadriparesis, and hypesthesia. There was no definite abnormality of language function, but detailed evaluation was impossible due to drowsiness. Initial funduscopic examination of the affected eye showed an attenuated cherry-red spot indicating central retinal artery occlusion combined with choroidal ischemia. The slit-lamp examination revealed corneal edema and cataract. Because of changes in the patient’s mental status, detailed ophthalmic examination, including fundus fluorescein angiography (FA), was impossible at the first visit and was performed 2 weeks later. Fundus FA showed significant delay of retinal and choroidal arterial perfusion that suggested total ophthalmic artery occlusion (Fig. 1A, B, D). Corneal edema and cataract was observed and obscured the view of the fundus photograph. Complete ptosis and total ophthalmoplegia was also observed in the left eye (Fig. 2). A brain diffusion MRI was performed one day after the symptom onset to rule out acute cerebral infarction, and it revealed numerous high signal intensity lesions in both cerebral hemispheres, mainly involving the left fronto-parieto-occipital lobes (Fig. 3A, B). Multiple territorial cerebral infarction lesions predominantly involving the cerebral cortex are considered to be of embolic etiology, rather than lacunar or thrombotic, which usually occur as a single or single territorial lesion and involve the subcortical white matter. In this patient, MRA showed no evidence of stenosis suggestive of atherosclerosis of cerebral large arteries, and no structural lesions or cardiac arrhythmia were observed using transthoracic echocardiography and 24-hour Holter monitoring. Therefore, it was considered that embolism caused by filler injection was the most likely cause of embolic cerebral infarction. Follow-up diffusion MRI on Day 7 revealed an extensive hemorrhagic transformation categorized as parenchymal hematoma noted in the previous infarcted foci (Fig. 3, D). Visual field examination revealed a right inferior quadrantanopia with macular sparing, presumably due to the left occipital lobe infarction (Fig. 4). To prevent exacerbation of inflammation caused by the filler material, methylprednisolone was administered at 1 g per day for a total of 5 days. Two weeks after the symptom onset, consciousness improved markedly. The limb weakness improved, but the right arm monoparesis remained. Six weeks later, she still lacked light perception in the left eye. Her ophthalmoplegia and ptosis in the left eye resolved but showed a mild limitation of abduction and depression. Corneal edema also resolved but the cataract had progressed. Six months later, there were no long-term complications, such as phthisis bulbi or rubeosis iridis. However, atrophic changes due to infarction were observed in both the inner and outer retinal layers and her vision had not improved. DISCUSSION Brain infarction is one of the most serious complications after cosmetic filler injection. However, very rare cases of bilateral embolic events, including cerebral infarction or IOAO, have been reported. We reviewed previous literature on IOAO associated with cosmetic facial filler injection and identified 4 more cases with bilateral embolic events (Table 1). In 3 cases, unilateral IOAO and bilateral cerebral infarction were identified, as in this case, and in one case, bilateral IOAO without cerebral infarction was identified. FIG. 1. A, B. Fluorescein angiography performed 2 weeks after the event showed a significant delay of left retinal and choroidal arterial perfusion (B, 1 minutes 54 seconds) compared with the right eye (A, 1 minutes 11 seconds). This suggests nearly complete occlusion of the left ophthalmic artery. The dotted circle indicates the location of the optic nerve head in the left eye. C. The time-of-flight MRA confirmed the presence of anterior communicating artery (arrow). D. Fundus photography performed 6 weeks after the event showed a diffuse atrophic change of the retina and choroid. Lee et al: J Neuro-Ophthalmol 2021; 41: e566-e571 e567 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. Clinical photographs taken on the day of event show marked limitation of left extraocular movement and left complete ptosis. Paik et al (13) reported a case of unilateral visual loss and ophthalmoplegia after injection of hyaluronic acid into the glabella. Brain diffusion MRI of this patient showed bilateral embolic brain infarction. Lin et al (11) reported a case of IOAO after nasal filler injection using hyaluronic acid. Multiple small infarctions over the bilateral hemisphere were noted in this case. Among the cases reported in our study group, a retrospective chart review confirmed one case of concomitant bilateral brain infarction after autologous fat injection in the glabella (1,3). Kim and Choi (14) reported a case of bilateral blindness due to ophthalmic artery occlusion after calcium hydroxyapatite filler injection for nose augmentation without brain infarction. There are 2 possible routes through which an embolism can be transmitted to the bilateral arterial system after facial filler injection as follows: 1) the anterior communicating artery and 2) cutaneous collaterals in the midline area between the right and left side. In our case, IOAO occurred only on the left side. According to the clinical manifestations and fundus FA FIG. 3. A, B. Brain diffusion MRI on Day 1 after facial filler injection showed the numerous high signal intensity lesions in both cerebral hemispheres, involving fronto-parieto-occipital lobes, which were acute embolic infarction caused by fillerrelated emboli. C, D. In follow-up diffusion MRI on Day 7, the extensive hemorrhagic transformation that could be categorized as parenchymal hematoma had been noted in the previous infarcted foci, especially in both frontal and left parieto-occipital lobes. e568 Lee et al: J Neuro-Ophthalmol 2021; 41: e566-e571 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 4. Visual field examination using the Humphrey field analyzer and 10-2 algorithm disclosed a right inferior quadrantanopia in the right eye due to the left occipital lobe infarction. findings, the embolic material caused the occlusion of the proximal part of the ophthalmic artery and could reach the internal carotid artery (ICA). Cerebral infarction mainly affected the left hemisphere, and relatively mild right cerebral infarction involved the anterior and middle cerebral artery territories. The channel that enables left–right communication between the left ICA and the right anterior and middle cerebral artery is the anterior communicating artery. In this patient, the presence of anterior communicating artery was confirmed using time-of-flight MRA (Fig. 1C), and we believe that injected hyaluronic acid was pushed proximally from cutaneous collaterals between the external carotid artery (ECA) and left ophthalmic artery to the left ICA and spread to the right cerebral hemisphere through the anterior communicating artery (Fig. 5A). The filler material fills the lumen of the proximal ophthalmic artery to reach the ipsilateral ICA. Complete occlusion of the proximal part of the ophthalmic artery not only blocks the arterial circulation of the retina and choroid but also inhibits blood flow to the anterior segment, extraocular muscles, eyelids, and skin. This condition could be classified as a type of “orbital infarction syndrome” and the cause of anterior segment ischemia (corneal edema and cataract), ptosis, and ophthalmoplegia. Another possible pathway of bilateral embolic propagation is through the cutaneous collaterals in the midline area. The frontal branches of the superficial temporal artery and the supratrochlear or supraorbital artery form a network of cutaneous collateral channels. Especially in the glabella and forehead area, numerous arterial anastomoses between the right and left cutaneous arterioles are known to exist (Fig. 5B). However, according to this hypothesis, the reason why the right cerebral infarction occurred without the right IOAO cannot be explained. In 4 cases (including our case in this article), in which unilateral IOAO and bilateral brain infarction occurred, the most probable pathway is through the anterior communicating artery (Fig. 5A). One case with bilateral IOAO without brain infarction most likely supports the second TABLE 1. Summary of the clinical characteristics of the patients with bilateral embolic events related to IOAO after cosmetic facial filler injections (our patients and previously reported cases from literature review) Author Year Age, yr Sex Underlying Disease Park et al (1) 2012 26 F None Autologous fat Glabella L CRAO N/A Kim et al (14) Paik et al (13) Lin et al (11) Our case 2013 30 M N/A Nose B OAO 2013 25 F None Calcium hydroxyapatite Hyaluronic acid Glabella R 2015 25 F None Hyaluronic acid Nose 2019 39 F None Hyaluronic acid Glabella Material Used Site Side Type of of IOAO IOAO Infarcted Territory Neurologic Sequelae N/A None L. MCA and B. ACA territories None None OAO Dizziness B. ACA N/A R CRAO None B. MCA N/A L OAO Mental change, dysarthria, quadriparesis, and hypesthesia Contralateral visual field defect B. ACA and MCA Neurologic Symptom Right arm monoparesis ACA, anterior cerebral artery; B, bilateral; CRAO, central retinal artery occlusion; F, female; IOAO, iatrogenic ophthalmic artery occlusion; L, left; M, male; MCA, middle cerebral artery; N/A, not applicable or mentioned; OAO, ophthalmic artery occlusion; R, right. Lee et al: J Neuro-Ophthalmol 2021; 41: e566-e571 e569 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 5. Possible mechanisms of bilateral propagation of embolic material after cosmetic facial filler injection. A, artery. hypothesis cutaneous arterial anastomosis between the right and left side (Fig. 5B). The case of bilateral IOAO without brain infarction is important evidence that bilateral embolic events and the clinical manifestations of filler-induced IOAO due to the second mechanism (cutaneous arterial anastomosis between the right and left side) clearly differ from the other 4 cases. In our case, no treatment was performed for reperfusion of the ophthalmic artery because of severe clinical features, including cerebral infarction, suggesting that a large amount of filler material caused extensive obstruction of the ophthalmic artery and its branches. It was suspected that the viability of the retina was lost, and cerebral infarction with mental change was a more serious problem. Hyaluronidase could be an additional treatment option. However, its effectiveness has not been proven in previous reports (15,16). Ischemic damage to the anterior segment and extraocular muscles could recover due to the relatively e570 good collateral blood circulation and viability of tissues, which are better than those of the retina. In this case, hemorrhagic transformation of the infarcted brain foci was found on follow-up MRI obtained on Day 7 (Fig. 3C, D). Although the cause of hemorrhagic transformation cannot be definitively clarified, considering that hemorrhagic transformation usually occurs after recanalization of occluded cerebral vessels in atherosclerotic ischemic stroke, spontaneous recanalization of multiple distal cerebral arteries, which were occluded by HA, may have induced hemorrhagic transformation. Further studies are warranted as to whether the properties of HA further accelerate hemorrhagic transformation. Ocular and nonocular manifestations and fundus FA findings of IOAO are important in predicting the extent of occluded vessels according to the suggested mechanism, retrograde filling of the involved arteriole by filler material, and subsequent dissemination and distal spreading of the Lee et al: J Neuro-Ophthalmol 2021; 41: e566-e571 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution embolic material to the other adjacent branches of the ophthalmic artery. In cases with brain infarction, the embolic material fills the proximal part of the ophthalmic artery before it reaches the ICA. Therefore, as in this case, it is more likely to be presented in the form of orbital infarction syndrome than in focal IOAO (selective central retinal artery occlusion or branch retinal artery occlusion). On the other hand, in cases of IOAO with focal occlusion of certain branches of the ophthalmic artery, the corresponding clinical features should be considered with the pattern and origin of branching vessels to predict the extent of occlusion. Moreover, anatomical variations should also be considered. For example, unusual variations, such as the ophthalmic artery arising from the middle meningeal artery or terminal of the external carotid artery (17,18), can cause unexpected clinical features. Although IOAO and associated brain infarction are rare complications, their potential should be explained to all patients considering this procedure. Once the embolic material has traveled to the ipsilateral brain, contralateral brain infarction through the anterior communicating artery is a distinct potentiality. In particular, even if unilateral IOAO occurs, the possibility of contralateral cerebral infarction should be considered. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: J. S. Lee and S. J. Woo; b. Acquisition of data: S. J. Woo; c. Analysis and interpretation of data: J. S. Lee, J. Y. Kim, and S. J. Woo. Category 2: a. Drafting the manuscript: J. S. Lee, J. Y. Kim, and S. J. Woo; b. Revising it for intellectual content: J. S. Lee, J. Y. Kim, and S. J. Woo. Category 3: a. Final approval of the completed manuscript: J. S. Lee, J. Y. Kim, and S. J. Woo. REFERENCES 1. Park SW, Woo SJ, Park KH, Huh JW, Jung C, Kwon OK. Iatrogenic retinal artery occlusion caused by cosmetic facial filler injections. Am J Ophthalmol. 2012;154:653–662.e651. 2. Park KH, Kim YK, Woo SJ, Kang SW, Lee WK, Choi KS, Kwak HW, Yoon IH, Huh K, Kim JW; Korean Retina Society. Iatrogenic occlusion of the ophthalmic artery after cosmetic facial filler injections: a national survey by the Korean Retina Society. JAMA Ophthalmol. 2014;132:714–723. Lee et al: J Neuro-Ophthalmol 2021; 41: e566-e571 3. Hong JH, Ahn SJ, Woo SJ, Jung C, Chang JY, Chung JH, Han MK. Central retinal artery occlusion with concomitant ipsilateral cerebral infarction after cosmetic facial injections. J Neurol Sci. 2014;346:310–314. 4. Egido JA, Arroyo R, Marcos A, Jimenez-Alfaro I. Middle cerebral artery embolism and unilateral visual loss after autologous fat injection into the glabellar area. Stroke. 1993;24:615–616. 5. Lee DH, Yang HN, Kim JC, Shyn KH. Sudden unilateral visual loss and brain infarction after autologous fat injection into nasolabial groove. Br J Ophthalmol. 1996;80:1026–1027. 6. Feinendegen DL, Baumgartner RW, Vuadens P, Schroth G, Mattle HP, Regli F, Tschopp H. Autologous fat injection for soft tissue augmentation in the face: a safe procedure? Aesthet Plast Surg. 1998;22:163–167. 7. Danesh-Meyer HV, Savino PJ, Sergott RC. Case reports and small case series: ocular and cerebral ischemia following facial injection of autologous fat. Arch Ophthalmol. 2001;119:777– 778. 8. Yoon SS, Chang DI, Chung KC. Acute fatal stroke immediately following autologous fat injection into the face. Neurology. 2003;61:1151–1152. 9. Lee KM, Kim EJ, Jahng GH, Chang DI. Magnetic resonance findings in two episodes of repeated cerebral fat embolisms in a patient with autologous fat injection into the face. J Korean Neurosurg Soc. 2012;51:312–315. 10. He MS, Sheu MM, Huang ZL, Tsai CH, Tsai RK. Sudden bilateral vision loss and brain infarction following cosmetic hyaluronic acid injection. JAMA Ophthalmol. 2013;131:1234– 1235. 11. Lin YC, Chen WC, Liao WC, Hsia TC. Central retinal artery occlusion and brain infarctions after nasal filler injection. QJM. 2015;108:731–732. 12. Ragam A, Agemy SA, Dave SB, Khorsandi AS, Banik R. Ipsilateral ophthalmic and cerebral infarctions after cosmetic polylactic acid injection into the forehead. J Neuroophthalmol. 2017;37:77–80. 13. Paik DW, Jang IB, Kim JS, Lee JH, Choi J. A case of visual loss and ophthalmoplegia following injection of hyaluronic acid into the glabella. J Korean Ophthalmological Soc. 2013;54:971– 976. 14. Kim YJ, Choi KS. Bilateral blindness after filler injection. Plast Reconstr Surg. 2013;131:298e–299e. 15. Carruthers J, Fagien S, Dolman P. Retro or peribulbar injection techniques to reverse visual loss after filler injections. Dermatol Surg. 2015;41(suppl 1):S354–S357. 16. Zhu GZ, Sun ZS, Liao WX, Cai B, Chen CL, Zheng HH, Zeng L, Luo SK. Efficacy of retrobulbar hyaluronidase injection for vision loss resulting from hyaluronic acid filler embolization. Aesthet Surg J. 2017;38:12–22. 17. Sabatier A, Robert PY, Sauvage JP, Bessede JP, Adenis JP, Chapot R. Ophthalmic arteries originating from external carotid arteries. J Fr Ophtalmol. 2006;29:e20. 18. Kimball D, Kimball H, Tubbs RS, Loukas M. Variant middle meningeal artery origin from the ophthalmic artery: a case report. Surg radiologic Anat. 2015;37:105–108. e571 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.