不可逆轉(zhuǎn)的失明之后眼周的自體富含血小板等離子皮膚再生療法

1、CASE REPORTS病理報告Irreversible Blindness Following Periocular Autologous Platelet-Rich Plasma Skin Rejuvenation Treatment 不可逆轉(zhuǎn)的失明之后眼周的自體富含血小板等離子皮膚再生療法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

2、Ji Liu, M.D. Krishnapriya Kalyam,醫(yī)學(xué)博士卡佛西,夏新,醫(yī)學(xué)博士,邁克爾埃利希?？死锼雇懈騰醫(yī)學(xué)博士,尼莎查達醫(yī)學(xué)博士莎拉Khodadadeh,醫(yī)學(xué)博士,和劉霽,醫(yī)學(xué)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 s

3、kin 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 infar

4、ction. 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歲的婦女發(fā)展敏銳的視力喪失在雙邊整容后的右眼富含血小板等離子體注入rhytids在眉間的地區(qū)。外部檢查在該地區(qū)顯示皮膚壞死rhytids和限制對眼部的能動性。擴張眼底檢查是重要的眼動脈阻塞。成像顯示右眼眼

5、外肌缺血和視神經(jīng)梗塞,右額葉,頂葉,和枕葉梗死。血栓栓塞的診斷檢查和血管性病因是負的。據(jù)我們所知,這是第一例報道廣泛的缺血自體富含血小板血漿治療。CASE REPORT 病理報告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 acu

6、te 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 fr

7、om 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 inje

8、ction 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

9、of vision in nasal field followed by complete loss of vision. 這里的案例報告是符合健康保險流通與責(zé)任法案(HIPAA)監(jiān)管。一個原本健康的49歲的女人向耶魯大學(xué)眼科中心抱怨急性右眼失明與嚴(yán)重的惡心和眼睛疼。一天之前,病人接受了自體富含血小板血漿(APRP)注射過程無證醫(yī)生減少皺紋雙邊眉間的地區(qū)。報道稱,血從她的肘前的區(qū)域通過靜脈穿刺和離心獲得濃縮自體血漿。雙邊額頭rhytids注射進行。病人不知道等離子體的細節(jié)準(zhǔn)備和用于注射針的大小。她容忍第一注入在左邊。然而,在第二次注射年底鼻右眉,她覺得針穿透略深,伴隨著她身后突然疼痛和豐滿的右

10、眼立即視覺損失在接下來的幾分鐘。然后她指出瞬態(tài)改善視力在鼻領(lǐng)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 hypotrop

11、ia 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

12、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 che

13、rry red spot suggested diffuse choroidal ischemia. No Hollenhorst plaque was seen. The left fundus exam was unremarkable. 檢查,視覺上沒有光感覺右眼和左眼的20/20。發(fā)音正確的瞳孔傳入障礙。右眼的能動性是限制supraduction和內(nèi)收導(dǎo)致右外斜視,在主要的目光下斜視。外部考試了1厘米面積瘀斑和硬化上面正確的內(nèi)側(cè)的額頭。眼皮都軟,沒有突出或抵抗后退。前部分是毋庸置疑的雙眼除了右眼溫和的結(jié)膜充血。眼壓在正常范圍內(nèi)雙邊。眼底檢查的右眼揭示深刻的視覺閥瓣蒼白,彌漫性視網(wǎng)膜美白

14、包括中央窩,明顯衰減的小動脈血管的突然結(jié)束midperiphery,中央黃斑水腫。缺乏一個櫻桃紅斑建議分散脈絡(luò)膜缺血。沒有Hollenhorst斑塊是觀察。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 mul

15、tiple 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

16、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. 頭部和頸部CT顯示右亞急性額葉沒有識別受損血管缺血。MRI和MR

17、A的腦部和軌道證明限制擴散沿正確的視神經(jīng)和多個亞急性梗死涉及右額葉、頂葉、枕葉(圖1)。不對稱異常天賦/ T2信號右側(cè)內(nèi)直肌的提示缺血(圖2)。右額骨內(nèi)骨髓水腫與不規(guī)則增強涉及覆蓋皮膚也顯示。MRA的大腦和頸部是消極的海綿竇病理學(xué),或椎或頸動脈解剖。CTA的頭部和頸部和經(jīng)胸廓的超聲心動圖發(fā)現(xiàn)沒有插子的起源。頸動脈多普勒超聲心動圖和消極。 Laboratory tests revealed mildly elevated erythrocyte sedimentation rate (26mm/h, normal 020), and C-reactive protein (3.8mg/L, no

18、rmal 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

19、factors, antineutrophil cytoplasmic antibody, and hemoglobin screen. 實驗室檢測顯示輕度升高紅細胞沉降率(26毫米/小時,正常0-20)和c反應(yīng)蛋白(3.8 mg / L,正常0.1 - -3.0)和一個正常的完整的血細胞計數(shù)測試。進一步檢查血栓性和arteritic過程都是負的,包括PT / PTT、印度盧比、Beta2glycoprotein,同型半胱氨酸,蛋白c和S,肺動脈栓塞,抗凝血酶III,心磷脂,jak2,C3,C4,Anti-DNA ab,狼瘡抗凝,類風(fēng)濕因子,antineutrophil胞質(zhì)抗體,屏幕和血紅蛋白

20、。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. Th

21、e 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 diffus

22、e 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

23、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). 病人被診斷為急性右眼動脈閉塞和腦梗塞的并發(fā)癥眶周的APRP注入。動脈內(nèi)的tPA到了窗外,她與眼部按摩治療,局部timolol brimonidine 0.2%

24、 0.5%,口服類固醇。病人拒絕前房穿刺術(shù)。她被靜脈注射抗生素可能感染引起眶周的腫脹和紅斑。外部和眼底攝影展示了瘀斑和缺血后1周的眉間的區(qū)域(圖3)和彌漫性視網(wǎng)膜美白和缺血(圖4)。本篇由第2周恢復(fù)正常。演示一年后,病人的右眼視力仍然沒有光感知與殘余右眉間的地區(qū)的疤痕和硬結(jié)節(jié)。病人后來疤痕修正手術(shù)一年后正確的眉間。疤痕組織的病理顯示lipid-based異物巨細胞反應(yīng),與以前的注入深度內(nèi)的異物是一致的組織(圖5)。DISCUSSION 討論Autologous platelet-rich plasma is obtained by centrifuging autologous blood u

25、ntil 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 pl

26、atelet alpha granules.14 Recently, physicians and cosmetologists across the country have been exploring its use as cosmetic filler for skin augmentation. 自體富含血小板血漿通過離心法自體血液,直到血漿血小板水平超過正常的血液。自體富含血小板血漿中常用的潰瘍,燒傷,傷口,脫發(fā),和面部復(fù)興的血管生成和膠原蛋白合成通過upregulation生長因子和細胞因子包含在血小板顆粒。全國1 - 4最近,醫(yī)德的醫(yī)生和精于偽造的一直在探索其作為皮膚的化妝品填

27、料增強。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 traditiona

28、l 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 injec

29、tion, 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. 有品種APRP基于他們的準(zhǔn)備過程和合成組件。例如,Leukocyte-rich PRP包含更多的白細

30、胞比傳統(tǒng)PRP孤立的雙重速度離心。富含血小板纖維蛋白基質(zhì)的血小板濃度低于傳統(tǒng)PRP包括等離子體和蛋白質(zhì)在一個更大的體積。這些變量可以使不同成分的氧自由基和溶酶體酶,以及生長因子濃度,釋放,和綁定的能力。一些實踐者故意修改這些產(chǎn)品注入之前,包括混合的PRP填充物。4病人拒絕透露聯(lián)系方式的從業(yè)者進行注射。因此,目前還不清楚如果這APRP產(chǎn)品是正確或改變之前的注入。FIG. 1. MRI brain: FLAIR image and DWI demonstrate ischemia of right frontal and parietal lobes (arrows). DWI, diffusio

31、n weighted image. 圖1所示。核磁共振成像的大腦:天賦形象和酒后駕駛證明缺血的右額葉和頂葉(箭頭)。醉酒駕車,擴散加權(quán)圖像。FIG. 2. MRI head and orbit: FLAIR and DWI images demonstrate right medial rectus ischemia. DWI, diffusion weighted image. 圖2所示。MRI頭和軌道:天賦和酒后駕駛圖片演示正確的內(nèi)側(cè)腹直肌缺血。醉酒駕車,擴散加權(quán)圖像。Autologous platelet-rich plasma therapy is relatively contrai

32、ndicated 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

33、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. 自體富含血小板血漿治療是相對禁忌的患者是在慢性antiagg

34、regant療法。5應(yīng)采取警告如果病人非甾體類抗炎藥的使用7到10天前程序,一個活躍的感染,全身使用糖皮質(zhì)激素在2周內(nèi)注入之前,和條件將病人置于hypercoagulative狀態(tài),如吸煙和使用口服避孕藥。過去的病史和藥物和解獲得APRP治療前應(yīng)該仔細。這個病人是不抽煙的,注射前并沒有服用任何藥物。Visual complications from various periocular synthetic cosmetic fillers have been previously reported.69 Recently, US Food and Drug Administration iss

35、ued 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

36、 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 (hyalu

37、ronic 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,

38、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

39、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

40、3 (18%) remained NLP.8 視覺各種并發(fā)癥眼周的合成化妝品填料曾被報導(dǎo)過。6 - 9最近,美國食品和藥物管理局發(fā)出安全警報視力喪失和中風(fēng)的風(fēng)險中等的無意注入軟組織填充面部血管。10自體富含血小板血漿不是經(jīng)常用作物理填充。效果通常是生長因子和其他物質(zhì)的結(jié)果包含或分泌血小板而不是物理填充效果。據(jù)我們所知,沒有視力喪失的報道與APRP當(dāng)用作填料。卡爾et al.6描述3患者突然失明后注入三種不同真皮填充物(透明質(zhì)酸、自體脂肪和牛膠原蛋白與有機玻璃微球混合)到前額區(qū)。他們推測,通過動脈逆行的填料流導(dǎo)致眼部缺血。研究表明通過視網(wǎng)膜逆行插子的旅行,眼科,通常頸內(nèi)動脈系統(tǒng)。11、12作者相

41、信類似的機制是視力喪失的病人負責(zé)。在一系列的44名患者中,并發(fā)眼和腦梗死發(fā)生在27%,最終視力NLP在61%的主題。與自體脂肪視覺預(yù)后最差。7在2012年的29日文章系統(tǒng)回顧描述32美容注射后視力喪失,患者的鼻唇(n = 7)和頭皮(n = 3)地區(qū)最常見的注射部位,其次是前額、眉間,臉頰,和寺廟。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

42、 plasma. 圖3所示。瘀斑和缺血的眉間的區(qū)域1星期后注入APRP rhytids。APRP,自體富含血小板血漿。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. 圖4所示。彩色眼底照片的右眼失明后1周后PRP,展示彌漫性視網(wǎng)膜美白和缺血。PRP,富含血小板血漿。FIG. 5. H&E stain of the

43、 right glabella scar tissue (400). The bold arrow shows the giant cell reaction for foreign bodies (thin arrow) within deep muscle layers. 圖5所示。)染色的眉間疤痕組織(400)。大膽的箭頭顯示了異物巨細胞反應(yīng)深肌層內(nèi)薄(箭頭)These reports highlight the importance of intimate understanding of facial vascular anatomy during cosmetic injectio

44、ns. 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 comprom

45、ise. 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 vascu

46、lar complications occur.14,15 這些報告強調(diào)親密的理解的重要性在注射美容面部血管解剖。APRP后患者的眼動脈阻塞的情況下是可以不經(jīng)意間發(fā)生的視力喪失傳統(tǒng)和新型化妝品材料。完整的平面的意識注入皮內(nèi)而不是皮下的可能有助于減少或消除血管妥協(xié)。吸氣注入之前,應(yīng)用局部血管收縮劑,用小針(30 - 32 G)技術(shù)和明智地使用壓力緩慢推薦的預(yù)防措施。8、11、13 - 15早期識別是重要的,直接的和積極的治療是授權(quán)應(yīng)該血管并發(fā)癥occur.14、15The authors hypothesize that the technique used in administering t

47、he 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, fro

48、m 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,

49、 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 placeme

50、nt 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. 作者假設(shè)技術(shù)用于管理APRP可能導(dǎo)致了視覺的并發(fā)癥。注射部位出現(xiàn)的接近眶上動脈和滑車上動脈,可能導(dǎo)致無意APRP注入到動脈。注射器的壓力可能導(dǎo)致逆行血小板凝塊的流,從眶上或滑車動脈近端分支,導(dǎo)致眼動脈的阻塞和其他地區(qū)的右大腦中

51、動脈,造成彌漫性缺血。缺血區(qū)域的眉間動脈栓塞的病人似乎相當(dāng)膚淺,表明可能并發(fā)靜脈阻塞。本篇有限,可以解釋為急性缺血性損傷眼外肌肉,這證實了成像。作者推斷的注射器沒有收回之前對血管內(nèi)注射針位置,這可能導(dǎo)致無意動脈內(nèi)的注入。支持的認(rèn)為病因是進一步負面的系統(tǒng)性檢查和正常超聲心動圖,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

52、 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. 皮膚結(jié)節(jié)狀

53、態(tài)在注射部位出現(xiàn)的有時是更多的問題與使用不當(dāng)?shù)奈锢硖畛湮铩Ｋ皇且粋€通常APRP注入后看到效果。然而,可憐的離心技術(shù)APRP或不當(dāng)?shù)幕旌咸盍峡梢孕纬裳舆t性的炎癥檢測不到發(fā)炎或跡象結(jié)節(jié)組織。15病理檢查確診的眉間疤痕在這個病人的深層組織內(nèi)異物的存在。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 r

54、egion 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.

55、 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. 結(jié)果在這種情況下,強調(diào)充分訓(xùn)練的重要性在新程序。作者建議謹(jǐn)慎采取注射填充物在眉間的

56、地區(qū)由于該地區(qū)豐富的血管供應(yīng),防止皮膚壞死或毀滅性的視覺的并發(fā)癥。此外,作者建議,眼周的注射由授權(quán)人員熟悉軌道解剖學(xué)和豐富的面部動脈吻合術(shù)。合格的從業(yè)人員都是訓(xùn)練有素,更能夠處理可能出現(xiàn)的并發(fā)癥。雖然眼外,填充注射可能導(dǎo)致毀滅性的視覺后果和意識和適當(dāng)?shù)男睦碜稍兊幕颊呤呛苤匾?。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 Sur

57、g 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

58、 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