不可逆转的失明之后眼周的自体富含血小板等离子皮肤再生疗法.docx

CASE REPORTS病理报告Irreversible Blindness Following Periocular Autologous Platelet-Rich Plasma Skin Rejuvenation Treatment 不可逆转的失明之后眼周的自体富含血小板等离子皮肤再生疗法Krishnapriya Kalyam, M.D., Shaheen C. Kavoussi, M.D., Michael Ehrlich, M.D., Christopher C. Teng, M.D., Nisha Chadha, M.D., Sarah Khodadadeh, M.D., and Ji Liu, M.D. Krishnapriya Kalyam,医学博士卡佛西,夏新,医学博士,迈克尔埃利希。克里斯托弗c腾医学博士,尼莎查达医学博士莎拉Khodadadeh,医学博士,和刘霁,医学博士Abstract: 摘要： A 49-year-old woman developed acute visual loss in the right eye following bilateral cosmetic platelet-rich plasma injections to rhytids in the glabellar region. External exam showed skin necrosis in the region over the right rhytids and restricted right ocular motility. Dilated fundus exam was significant for ophthalmic artery occlusion. Imaging revealed right eye extraocular muscle ischemia and optic nerve infarction, along with right frontal, parietal, and occipital lobe infarction. Work-up for thromboembolic and vascular etiologies were negative. To our knowledge, this is the first case reported of extensive ischemia following autologous platelet-rich plasma therapy. 49岁的妇女发展敏锐的视力丧失在双边整容后的右眼富含血小板等离子体注入rhytids在眉间的地区。外部检查在该地区显示皮肤坏死rhytids和限制对眼部的能动性。扩张眼底检查是重要的眼动脉阻塞。成像显示右眼眼外肌缺血和视神经梗塞,右额叶,顶叶,和枕叶梗死。血栓栓塞的诊断检查和血管性病因是负的。据我们所知,这是第一例报道广泛的缺血自体富含血小板血浆治疗。CASE REPORT 病理报告The case reported here is in compliance with the Health Insurance Portability and Accountability Act (HIPAA) regulation. An otherwise healthy 49-year-old woman presented to the Yale Eye Center complaining of acute loss of vision in the right eye associated with severe nausea and eye pain. One day prior, the patient underwent an autologous platelet-rich plasma (APRP) injection procedure by an unlicensed practitioner to reduce wrinkles in the glabellar region bilaterally. She reported that blood was taken from her antecubital region by venous puncture and centrifuged to obtain concentrated autologous plasma. Bilateral forehead rhytids injections were performed. The patient was unaware the details of the plasma preparation and the size of needle that was used for injections. She tolerated the first injection on the left side well. However, during the second injection at the nasal end of right eyebrow, she felt the needle penetrate slightly deeper, accompanied by sudden pain and fullness behind her right eye with immediate visual loss over the next few minutes. She then noted transient improvement of vision in nasal field followed by complete loss of vision. 这里的案例报告是符合健康保险流通与责任法案(HIPAA)监管。一个原本健康的49岁的女人向耶鲁大学眼科中心抱怨急性右眼失明与严重的恶心和眼睛疼。一天之前,病人接受了自体富含血小板血浆(APRP)注射过程无证医生减少皱纹双边眉间的地区。报道称,血从她的肘前的区域通过静脉穿刺和离心获得浓缩自体血浆。双边额头rhytids注射进行。病人不知道等离子体的细节准备和用于注射针的大小。她容忍第一注入在左边。然而,在第二次注射年底鼻右眉,她觉得针穿透略深,伴随着她身后突然疼痛和丰满的右眼立即视觉损失在接下来的几分钟。然后她指出瞬态改善视力在鼻领域完全失明。 On examination, vision was no light perception in the right eye and 20/20 in the left eye. A pronounced right afferent pupillary defect was present. Motility of the right eye was restricted in supraduction and adduction resulting in a right exotropia and hypotropia in primary gaze. External exam demonstrated a 1cm area of ecchymosis and induration above the right medial brow. The eyelids were soft and there was no proptosis or resistance to retropulsion. Anterior segment exam was unremarkable in both eyes except moderate conjunctival hyperemia in the right eye. Intraocular pressure was within normal limits bilaterally. Fundus exam of the right eye revealed profound optic disc pallor, diffuse retinal whitening including fovea, marked attenuation of arterioles with abrupt ending of the vessels in midperiphery, and central macular edema. Absence of a cherry red spot suggested diffuse choroidal ischemia. No Hollenhorst plaque was seen. The left fundus exam was unremarkable. 检查,视觉上没有光感觉右眼和左眼的20/20。发音正确的瞳孔传入障碍。右眼的能动性是限制supraduction和内收导致右外斜视,在主要的目光下斜视。外部考试了1厘米面积瘀斑和硬化上面正确的内侧的额头。眼皮都软,没有突出或抵抗后退。前部分是毋庸置疑的双眼除了右眼温和的结膜充血。眼压在正常范围内双边。眼底检查的右眼揭示深刻的视觉阀瓣苍白,弥漫性视网膜美白包括中央窝,明显衰减的小动脉血管的突然结束midperiphery,中央黄斑水肿。缺乏一个樱桃红斑建议分散脉络膜缺血。没有Hollenhorst斑块是观察。左眼底是毋庸置疑。Head and neck CT showed right subacute frontal lobe ischemia without identifiable compromised vessels. MRI/MRA of brain and orbit demonstrated restricted diffusion along the course of the right optic nerve and multiple subacute infarcts involving right frontal, parietal, and occipital lobes (Fig. 1). Asymmetric abnormal FLAIR/T2 signal of the right medial rectus muscle was suggestive of ischemia (Fig. 2). Bone marrow edema within the right frontal bone with irregular enhancement involving the overlying skin was also shown. MRA of the brain and neck was negative for cavernous sinus pathology, or vertebral or carotid artery dissection. CTA of the head and neck and transthoracic echocardiogram identified no embolic origin. Echocardiogram and carotid dopplers were negative. 头部和颈部CT显示右亚急性额叶没有识别受损血管缺血。MRI和MRA的脑部和轨道证明限制扩散沿正确的视神经和多个亚急性梗死涉及右额叶、顶叶、枕叶(图1)。不对称异常天赋/ T2信号右侧内直肌的提示缺血(图2)。右额骨内骨髓水肿与不规则增强涉及覆盖皮肤也显示。MRA的大脑和颈部是消极的海绵窦病理学,或椎或颈动脉解剖。CTA的头部和颈部和经胸廓的超声心动图发现没有插子的起源。颈动脉多普勒超声心动图和消极。 Laboratory tests revealed mildly elevated erythrocyte sedimentation rate (26mm/h, normal 020), and C-reactive protein (3.8mg/L, normal 0.13.0) with a normal complete blood count test. Further work-up for thrombotic and arteritic processes were all negative, including PT/PTT, INR, Beta2glycoprotein, homocysteine, protein-C and S, D-dimer, antithrombin III, cardiolipin, jak2, C3, C4, Anti-DNA ab, Lupus anticoagulant, rheumatoid factors, antineutrophil cytoplasmic antibody, and hemoglobin screen. 实验室检测显示轻度升高红细胞沉降率(26毫米/小时,正常0-20)和c反应蛋白(3.8 mg / L,正常0.1 - -3.0)和一个正常的完整的血细胞计数测试。进一步检查血栓性和arteritic过程都是负的,包括PT / PTT、印度卢比、Beta2glycoprotein,同型半胱氨酸,蛋白c和S,肺动脉栓塞,抗凝血酶III,心磷脂,jak2,C3,C4,Anti-DNA ab,狼疮抗凝,类风湿因子,antineutrophil胞质抗体,屏幕和血红蛋白。The patient was diagnosed with acute right ophthalmic artery occlusion and brain infarction as a complication of periorbital APRP injection. Having arrived outside the window of intra-arterial tPA, she was treated with ocular massage, topical timolol 0.5% and brimonidine 0.2%, and oral steroids. The patient declined anterior chamber paracentesis. She was given intravenous antibiotics for possible infectious cause of periorbital swelling and erythema. External and fundus photography 1 week after presentation demonstrated ecchymosis and ischemia of the right glabellar region (Fig. 3) and diffuse retinal whitening and ischemia (Fig. 4). Ocular motility returned to normal by week 2. One year after presentation, the patients vision remained no light perception in the right eye with residual scarring and hard nodules of the right glabellar region. Patient subsequently underwent scar revision surgery of the right glabella a year later. The pathology of scar tissue showed lipid-based foreign body with giant cell reaction that was consistent with prior injection of foreign material within deep tissues (Fig. 5). 病人被诊断为急性右眼动脉闭塞和脑梗塞的并发症眶周的APRP注入。动脉内的tPA到了窗外,她与眼部按摩治疗,局部timolol brimonidine 0.2% 0.5%,口服类固醇。病人拒绝前房穿刺术。她被静脉注射抗生素可能感染引起眶周的肿胀和红斑。外部和眼底摄影展示了瘀斑和缺血后1周的眉间的区域(图3)和弥漫性视网膜美白和缺血(图4)。本篇由第2周恢复正常。演示一年后,病人的右眼视力仍然没有光感知与残余右眉间的地区的疤痕和硬结节。病人后来疤痕修正手术一年后正确的眉间。疤痕组织的病理显示lipid-based异物巨细胞反应,与以前的注入深度内的异物是一致的组织(图5)。DISCUSSION 讨论Autologous platelet-rich plasma is obtained by centrifuging autologous blood until the plasma platelet level exceeds that of normal blood. Autologous platelet-rich plasma is commonly used in the setting of ulcers, burns, wounds, hair loss, and facial rejuvenation by way of angiogenesis and collagen synthesis through upregulation of growth factors and cytokines contained in platelet alpha granules.14 Recently, physicians and cosmetologists across the country have been exploring its use as cosmetic filler for skin augmentation. 自体富含血小板血浆通过离心法自体血液,直到血浆血小板水平超过正常的血液。自体富含血小板血浆中常用的溃疡,烧伤,伤口,脱发,和面部复兴的血管生成和胶原蛋白合成通过upregulation生长因子和细胞因子包含在血小板颗粒。全国1 - 4最近,医德的医生和精于伪造的一直在探索其作为皮肤的化妆品填料增强。There are varieties of APRP based on their preparation process and resultant components. For instance, Leukocyte-rich PRP contains more white blood cells than traditional PRP isolated by dual speed centrifugation. Platelet-rich fibrin matrix has a lower concentration of platelets than traditional PRP by including plasma and proteins in a larger volume. These variables can make difference in the ingredients of oxygen-free radicals and lysosomal enzymes, as well as growth factor concentrations, release, and binding abilities. Some practitioners deliberately modify these products before injection, including mixing the PRP with fillers.4 The patient declined to disclose the contact information of the practitioner who performed the injection. Therefore, it was unclear if this APRP product was made properly or altered before the injection. 有品种APRP基于他们的准备过程和合成组件。例如,Leukocyte-rich PRP包含更多的白细胞比传统PRP孤立的双重速度离心。富含血小板纤维蛋白基质的血小板浓度低于传统PRP包括等离子体和蛋白质在一个更大的体积。这些变量可以使不同成分的氧自由基和溶酶体酶,以及生长因子浓度,释放,和绑定的能力。一些实践者故意修改这些产品注入之前,包括混合的PRP填充物。4病人拒绝透露联系方式的从业者进行注射。因此,目前还不清楚如果这APRP产品是正确或改变之前的注入。FIG. 1. MRI brain: FLAIR image and DWI demonstrate ischemia of right frontal and parietal lobes (arrows). DWI, diffusion weighted image. 图1所示。核磁共振成像的大脑:天赋形象和酒后驾驶证明缺血的右额叶和顶叶(箭头)。醉酒驾车,扩散加权图像。FIG. 2. MRI head and orbit: FLAIR and DWI images demonstrate right medial rectus ischemia. DWI, diffusion weighted image. 图2所示。MRI头和轨道:天赋和酒后驾驶图片演示正确的内侧腹直肌缺血。醉酒驾车,扩散加权图像。Autologous platelet-rich plasma therapy is relatively contraindicated in patients who is under chronic antiaggregant therapy.5 Cautions should be taken if the patient has nonsteroidal anti-inflammatory drug usage 7 to 10 days before the procedure, an active infection, systemic use of corticosteroids within 2 weeks before injection, and conditions putting the patient in a hypercoagulative state, such as smoking and oral contraceptive use. Past medical history and medication reconciliation should be carefully obtained before APRP treatment. This patient was a nonsmoker and was not taking any medications before the injection. 自体富含血小板血浆治疗是相对禁忌的患者是在慢性antiaggregant疗法。5应采取警告如果病人非甾体类抗炎药的使用7到10天前程序,一个活跃的感染,全身使用糖皮质激素在2周内注入之前,和条件将病人置于hypercoagulative状态,如吸烟和使用口服避孕药。过去的病史和药物和解获得APRP治疗前应该仔细。这个病人是不抽烟的,注射前并没有服用任何药物。Visual complications from various periocular synthetic cosmetic fillers have been previously reported.69 Recently, US Food and Drug Administration issued a safety alert on the risks of visual loss and stroke secondary to the unintentional soft tissue filler injection into facial blood vessels.10 Autologous platelet-rich plasma is not often used as a physical filler. The effects are usually the result of growth factors and other material contained or secreted by platelets rather than the physical filling effects. To our knowledge, there have been no reports of vision loss associated with APRP when used as a filler. Carle et al.6 described 3 patients who presented with sudden loss of vision after injection of 3 different dermal fillers (hyaluronic acid, autologous fat, and bovine collagen mixed with polymethylmethacrylate microspheres) into the forehead area.They hypothesized that retrograde flow of fillers through arteries resulted in ocular ischemia. Studies have demonstrated retrograde embolic travel through the retinal, ophthalmic, and often internal carotid arterial systems.11,12 The authors believe that a similar mechanism was responsible for vision loss in the patient. In a series of 44 patients, concurrent ocular and brain infarctions occurred in 27% and final visual acuity was NLP in 61% of subjects. Visual prognosis was worst with autologous fat.7 In a 2012 systematic review of 29 articles describing 32 patients with visual loss following cosmetic injections, the nasolabial (n = 7) and scalp (n = 3) areas were the most common injection sites, followed by the forehead, glabella, cheek, and temples. All patients but 3 (18%) remained NLP.8 视觉各种并发症眼周的合成化妆品填料曾被报导过。6 - 9最近,美国食品和药物管理局发出安全警报视力丧失和中风的风险中等的无意注入软组织填充面部血管。10自体富含血小板血浆不是经常用作物理填充。效果通常是生长因子和其他物质的结果包含或分泌血小板而不是物理填充效果。据我们所知,没有视力丧失的报道与APRP当用作填料。卡尔et al.6描述3患者突然失明后注入三种不同真皮填充物(透明质酸、自体脂肪和牛胶原蛋白与有机玻璃微球混合)到前额区。他们推测,通过动脉逆行的填料流导致眼部缺血。研究表明通过视网膜逆行插子的旅行,眼科,通常颈内动脉系统。11、12作者相信类似的机制是视力丧失的病人负责。在一系列的44名患者中,并发眼和脑梗死发生在27%,最终视力NLP在61%的主题。与自体脂肪视觉预后最差。7在2012年的29日文章系统回顾描述32美容注射后视力丧失,患者的鼻唇(n = 7)和头皮(n = 3)地区最常见的注射部位,其次是前额、眉间,脸颊,和寺庙。所有患者但是3(18%)仍然NLP.8FIG. 3. Ecchymosis and ischemia of right glabellar region 1 week after injection of APRP to rhytids. APRP, autologous platelet-rich plasma. 图3所示。瘀斑和缺血的眉间的区域1星期后注入APRP rhytids。APRP,自体富含血小板血浆。FIG. 4. Color fundus photo of right eye taken 1 week after vision loss following PRP, demonstrating diffuse retinal whitening and ischemia. PRP, platelet-rich plasma. 图4所示。彩色眼底照片的右眼失明后1周后PRP,展示弥漫性视网膜美白和缺血。PRP,富含血小板血浆。FIG. 5. H&E stain of the right glabella scar tissue (400). The bold arrow shows the giant cell reaction for foreign bodies (thin arrow) within deep muscle layers. 图5所示。)染色的眉间疤痕组织(400)。大胆的箭头显示了异物巨细胞反应深肌层内薄(箭头)These reports highlight the importance of intimate understanding of facial vascular anatomy during cosmetic injections. The patients case of ophthalmic artery occlusion following APRP exemplifies the visual loss that can inadvertently occur with both traditional and novel cosmetic materials. Full awareness of injection plane to be intradermally rather than subdermally may help reduce or eliminate vascular compromise. Aspirating before injection, applying topical vasoconstrictors, and using smaller needles (30 to 32 G) with slow technique and judicious use of pressure are recommended precautionary measures.8,11,1315 Early recognition is important and immediate and aggressive treatment is mandate should vascular complications occur.14,15 这些报告强调亲密的理解的重要性在注射美容面部血管解剖。APRP后患者的眼动脉阻塞的情况下是可以不经意间发生的视力丧失传统和新型化妆品材料。完整的平面的意识注入皮内而不是皮下的可能有助于减少或消除血管妥协。吸气注入之前,应用局部血管收缩剂,用小针(30 - 32 G)技术和明智地使用压力缓慢推荐的预防措施。8、11、13 - 15早期识别是重要的,直接的和积极的治疗是授权应该血管并发症occur.14、15The authors hypothesize that the technique used in administering the APRP may have contributed to the visual complications. The site of injection was close to superior orbital artery and superior trochlear artery, presumably causing inadvertent injection of APRP into the artery. Pressure from the syringe likely resulted in retrograde flow of the platelet clot, from the superior orbital or trochlear artery to proximal branches, resulting in occlusion of the ophthalmic artery and other regions of the right middle cerebral artery, which caused diffuse ischemia. Ischemic area of the glabella in this patient seemed rather superficial for an arterial embolization, indicating possible concurrent vein occlusion. The limited ocular motility can be explained by the acute ischemic injury to the extraocular muscles, which was confirmed by imaging. The authors infer that the syringe was not drawn back upon before injection to assess for intravascular needle placement and this may have led to inadvertent intra-arterial injection. The presumed etiology is further supported by negative systemic work-up and normal echocardiogram, MRA, and CTA imaging. 作者假设技术用于管理APRP可能导致了视觉的并发症。注射部位出现的接近眶上动脉和滑车上动脉,可能导致无意APRP注入到动脉。注射器的压力可能导致逆行血小板凝块的流,从眶上或滑车动脉近端分支,导致眼动脉的阻塞和其他地区的右大脑中动脉,造成弥漫性缺血。缺血区域的眉间动脉栓塞的病人似乎相当肤浅,表明可能并发静脉阻塞。本篇有限,可以解释为急性缺血性损伤眼外肌肉,这证实了成像。作者推断的注射器没有收回之前对血管内注射针位置,这可能导致无意动脉内的注入。支持的认为病因是进一步负面的系统性检查和正常超声心动图,MRA和CTA成像。Skin nodularity at the site of injection is sometimes more problematic with improper use of physical fillers. It is not a usually seen effect after APRP injection. However, poor centrifugation technique of APRP or improper mixing of fillers can form delayed onset inflammatory or noninflammatory nodules of the tissues.15 The pathological exam of the glabella scar in this patient confirmed the presence of foreign bodies within the deep tissues. 皮肤结节状态在注射部位出现的有时是更多的问题与使用不当的物理填充物。它不是一个通常APRP注入后看到效果。然而,可怜的离心技术APRP或不当的混合填料可以形成延迟性的炎症检测不到发炎或迹象结节组织。15病理检查确诊的眉间疤痕在这个病人的深层组织内异物的存在。The findings in this case emphasize the importance of adequate training in new procedures. The authors recommend that caution be taken when injecting fillers in the glabellar region due to the rich vascular supply in this region and to prevent skin necrosis or devastating visual complications. Furthermore, the authors suggest that periocular injections be performed by licensed practitioners who are familiar with orbital anatomy and the rich anastomosis of facial arteries. Qualified practitioners are highly trained and are more capable to deal with complications that may arise. While extraocular in nature, filler injections can cause devastating visual consequences and awareness and proper counseling of patients is important. 结果在这种情况下,强调充分训练的重要性在新程序。作者建议谨慎采取注射填充物在眉间的地区由于该地区丰富的血管供应,防止皮肤坏死或毁灭性的视觉的并发症。此外,作者建议,眼周的注射由授权人员熟悉轨道解剖学和丰富的面部动脉吻合术。合格的从业人员都是训练有素,更能够处理可能出现的并发症。虽然眼外,填充注射可能导致毁灭性的视觉后果和意识和适当的心理咨询的患者是很重要的。REFERENCES引用1. Sommeling CE, Heyneman A, Hoeksema H, et al. The use of platelet-rich plasma in plastic surgery: a systematic review. J Plast Reconstr Aesthet Surg 2013;66:30111. 2. Sclafani AP, McCormick SA. Induction of dermal collagenesis, angiogenesis, and adipogenesis in human skin by injection of platelet-rich fibrin matrix. Arch Facial Plast Surg 2012;14:1326. 3. Andia I, Abate M. Platelet-rich plasma: underlying biology and clinical correlates. Regen Med 2013;8:64558. 4. Sclafani AP, Azzi J. Platelet preparations for use in facial rejuvenation and wound healing: a critical review of current literature. Aesthetic Plast Surg 2015;39:495505. 5. Di Matteo B, Filardo G, Lo Presti M, et al. Chronic anti-platelet therapy: a contraindication for platelet-rich plasma intra-articular injections? Eur Rev Med Pharmacol Sci 2014;18(1 Suppl):559. 6. Carle MV, Roe R, Novack R, et al. Cosmetic facial fillers and severe vision loss. JAMA Ophthalmol 2014;132:6379. 7. Park KH, Kim YK, Woo SJ, et al.; Korean Retina Society. Iatrogenic occlusion of the ophth