宋爽 喻曉兵※ 戴虹 陳沁 孫亮 朱小泉 原惠萍 楊帆 楊澤
脈絡(luò)膜厚度與老年性黃斑病變關(guān)系的研究進(jìn)展
宋爽1喻曉兵1※戴虹1陳沁1孫亮2朱小泉2原惠萍2楊帆2楊澤2
黃斑病變是多種眼底異常改變引起的黃斑疾病的總稱,其嚴(yán)重影響老年患者視功能及生活質(zhì)量,嚴(yán)重者引起失明,喪失生活自理能力。脈絡(luò)膜因血流豐富、代謝旺盛,直接或間接參與了多種老年性黃斑疾病的病理生理過(guò)程,脈絡(luò)膜厚度分析對(duì)黃斑疾病的診斷、治療及預(yù)后觀察均有一定的提示意義。本文針對(duì)脈絡(luò)膜厚度與老年性黃斑病變的關(guān)系進(jìn)行綜述。
脈絡(luò)膜厚度 老年黃斑病變
黃斑區(qū)的營(yíng)養(yǎng)主要由脈絡(luò)膜血管供給,脈絡(luò)膜的異??蓪?dǎo)致多種黃斑疾病。由于脈絡(luò)膜位于視網(wǎng)膜后面,常規(guī)的檢查儀器很難檢測(cè)脈絡(luò)膜全層結(jié)構(gòu),導(dǎo)致該領(lǐng)域的研究進(jìn)展緩慢。隨著頻域相干光斷層深度增強(qiáng)成像(EDI SD-OCT)技術(shù)的出現(xiàn),深層的脈絡(luò)膜結(jié)構(gòu)得以清晰地呈現(xiàn),并可以測(cè)量脈絡(luò)膜全層厚度,這對(duì)于臨床及科研工作者進(jìn)一步研究脈絡(luò)膜相關(guān)疾病的發(fā)病機(jī)制有著重大幫助。脈絡(luò)膜因血流豐富、代謝旺盛,直接或間接地參與了多種老年性黃斑疾病的病理生理過(guò)程,包括年齡相關(guān)性黃斑變性、息肉樣脈絡(luò)膜血管病變、糖尿病視網(wǎng)膜病變、中心性滲出性脈絡(luò)膜視網(wǎng)膜病變、中心性漿液性脈絡(luò)膜視網(wǎng)膜病變、葡萄膜炎、高度近視等。脈絡(luò)膜厚度分析對(duì)黃斑疾病的診斷、治療及預(yù)后觀察均有一定的提示意義,因此探討脈絡(luò)膜厚度與老年性黃斑疾病的關(guān)系成為當(dāng)今眼科領(lǐng)域的研究熱點(diǎn)?,F(xiàn)就脈絡(luò)膜厚度與老年性黃斑病變的關(guān)系綜述如下。
脈絡(luò)膜構(gòu)成葡萄膜的最后部,位于視網(wǎng)膜色素上皮層與鞏膜的棕黑板層之間。脈絡(luò)膜包含血管、黑色素細(xì)胞、成纖維細(xì)胞、免疫活性細(xì)胞、支持膠原、富彈性結(jié)締組織,即主要成分由3層血管組織構(gòu)成:靠近視網(wǎng)膜的毛細(xì)血管層、臨近鞏膜的大血管層(Haller層)及兩層之間的中血管層(Sattler層)。脈絡(luò)膜是人體內(nèi)代謝最活躍的組織之一,主要的生理功能如下:其血液占眼球內(nèi)血液總量的90%,其中70%在毛細(xì)血管層;為外層2/3視網(wǎng)膜提供營(yíng)養(yǎng)物質(zhì)與氧氣;通過(guò)黃斑中心凹區(qū)域的聚光作用傳遞熱量并調(diào)節(jié)眼內(nèi)溫度;豐富的色素細(xì)胞的遮光暗房作用使物象更清楚;分泌多種因子調(diào)節(jié)血管化及鞏膜的生長(zhǎng)[1]。
脈絡(luò)膜的解剖及生理功能提示其在黃斑部疾病發(fā)生發(fā)展中具有重要作用,脈絡(luò)膜血管豐富,尤其是視細(xì)胞豐富、對(duì)氧需求量較大的黃斑區(qū),脈絡(luò)膜自身的血管阻力、血管通透性、血流量和滲透壓的改變及神經(jīng)體液調(diào)節(jié)都可能影響脈絡(luò)膜厚度[2]。傳統(tǒng)的脈絡(luò)膜厚度研究方法為組織切片染色,但組織的準(zhǔn)備、固定過(guò)程可能導(dǎo)致離體眼組織切片下脈絡(luò)膜厚度與活體脈絡(luò)膜的真實(shí)厚度差異較大。Spaide等[3]首次報(bào)道了活體非侵入性的脈絡(luò)膜厚度檢測(cè)方法,即加強(qiáng)模式的頻域OCT技術(shù)(enhanced depth imaging spectral-domain optical coherence tomography,EDI SD-OCT),其在傳統(tǒng)SD-OCT的基礎(chǔ)上將設(shè)備進(jìn)一步靠近受檢眼,使更多的光線集中照射在脈絡(luò)膜內(nèi)部甚至更深的鞏膜水平,從而得到清晰的脈絡(luò)膜斷層圖像。該技術(shù)使在體觀察黃斑部脈絡(luò)膜厚度成為可能,目前對(duì)于脈絡(luò)膜厚度的測(cè)量主要定位于黃斑中心凹下。北京眼病研究所通過(guò)對(duì)3233人的大樣本研究發(fā)現(xiàn)[4],EDI SD-OCT對(duì)于黃斑部脈絡(luò)膜厚度測(cè)量有良好的一致性與可靠性,使其為臨床及科研工作者進(jìn)一步研究脈絡(luò)膜相關(guān)疾病的發(fā)病機(jī)制及分析脈絡(luò)膜厚度對(duì)眼部疾病的診斷、治療及預(yù)后觀察提供巨大幫助。既往針對(duì)正常人的脈絡(luò)膜厚度研究發(fā)現(xiàn)[5,6],50歲以上人群隨著年齡的增加,脈絡(luò)膜厚度逐漸變薄,此外,眼軸越長(zhǎng)、屈光度越高的患者脈絡(luò)膜厚度越薄。
3.1 脈絡(luò)膜厚度與滲出性年齡相關(guān)性黃斑變性 滲出性年齡相關(guān)性黃斑變性(exudative age-related macular degeneration,AMD)是引起50歲以上人群視力不可逆性喪失的主要原因[7],脈絡(luò)膜新生血管(choroidal neovascularization,CNV)的形成是滲出性AMD的病理基礎(chǔ)[8]。Maruko等對(duì)日本人群進(jìn)行調(diào)查發(fā)現(xiàn),滲出性AMD患者中35%為經(jīng)典型AMD,55%為息肉樣脈絡(luò)膜血管病變(polypoidal choroidal vasculopathy,PCV)[9],其主要表現(xiàn)為眼底后極部橘黃色隆起,眼底吲哚青綠造影可見(jiàn)脈絡(luò)膜血管末端息肉樣膨大及異常的分支血管網(wǎng)。PCV對(duì)于光動(dòng)力(photodynamic therapy,PDT)治療效果較好[10],而抗VEGF治療并不能使息肉樣病變消退[11]。但對(duì)于經(jīng)典型AMD,抗VEGF的療效要優(yōu)于PDT治療[12]。因此,臨床中能有效、準(zhǔn)確、安全的鑒別兩者,將對(duì)臨床醫(yī)生進(jìn)行臨床決策時(shí)提供重要的依據(jù),為患者減輕經(jīng)濟(jì)負(fù)擔(dān),為社會(huì)節(jié)約醫(yī)療資源。
近年來(lái),利用EDI SD-OCT技術(shù),日本學(xué)者Jirarattanasopa等[13]發(fā)現(xiàn)PCV患者的脈絡(luò)膜厚度明顯較經(jīng)典型AMD患者厚,此外該研究還發(fā)現(xiàn),經(jīng)過(guò)PDT聯(lián)合玻璃體腔雷珠單抗(ranibizumab)治療后,脈絡(luò)膜厚度明顯變薄。同樣的,Maruko等[14]也發(fā)現(xiàn),經(jīng)過(guò)PDT治療后,PCV患者黃斑中心凹下脈絡(luò)膜厚度明顯變薄。Jirarattanasopa等認(rèn)為,對(duì)于脈絡(luò)膜厚度較薄的經(jīng)典型AMD患者,考慮其可能的并發(fā)癥,PDT治療需慎重。因此,Jirarattanasopa等相信,對(duì)于脈絡(luò)膜血管通透性正常的患者,EDI SD-OCT對(duì)鑒別經(jīng)典型AMD和PCV及指導(dǎo)個(gè)體化治療有著重要的輔助診斷價(jià)值。
3.2 脈絡(luò)膜厚度與糖尿病視網(wǎng)膜病變 糖尿病視網(wǎng)膜病變(diabetic retinopathy,DR)是糖尿病在眼部最常見(jiàn)的并發(fā)癥,隨著全球糖尿病患病率的增加,糖尿病視網(wǎng)膜病變已成為首位危害視力的視網(wǎng)膜血管性疾?。?5]。組織學(xué)研究表明,DR患者的脈絡(luò)膜病理改變與視網(wǎng)膜病變相關(guān)[16]。DR的發(fā)病機(jī)制主要與血視網(wǎng)膜屏障破壞和血流動(dòng)力學(xué)異常有關(guān)[17,18],DR早期脈絡(luò)膜血流減低,伴有黃斑水腫的患者更為顯著[19]。脈絡(luò)膜厚度是脈絡(luò)膜在體研究形態(tài)學(xué)改變的重要指標(biāo),對(duì)DR的病理變化及治療、預(yù)后有一定的指導(dǎo)意義。利用EDI SD-OCT技術(shù),Kim等[20]通過(guò)對(duì)235名2型糖尿病患者脈絡(luò)膜厚度測(cè)量后發(fā)現(xiàn),隨著DR病情的加重,脈絡(luò)膜厚度明顯增加,合并視網(wǎng)膜下脫離的糖尿病性黃斑水腫的患者脈絡(luò)膜厚度增加最顯著,而經(jīng)過(guò)全視網(wǎng)膜光凝治療后的患者脈絡(luò)膜厚度明顯變薄。因此,Kim等推測(cè),DR患者的VEGF或其他炎癥因子含量增加,引起脈絡(luò)膜血管舒張,進(jìn)而增加脈絡(luò)膜血流灌注,最終引起脈絡(luò)膜血管層厚度增加;而經(jīng)光凝治療后的DR患者脈絡(luò)膜厚度降低與VEGF含量下降有關(guān),大多數(shù)研究者得出的結(jié)論與此相同,但少數(shù)學(xué)者的研究結(jié)論相反。Vujosevic等[21]通過(guò)對(duì)102名糖尿病患者及48名正常對(duì)照進(jìn)行脈絡(luò)膜測(cè)量,Sayin等[22]通過(guò)測(cè)量41名1型糖尿病兒童與42名正常兒童的脈絡(luò)膜厚度,兩個(gè)研究均發(fā)現(xiàn)脈絡(luò)膜厚度與糖尿病視網(wǎng)膜病變無(wú)明顯相關(guān)性。此外小部分研究因未對(duì)DR患者是否接受光凝治療進(jìn)行區(qū)分,測(cè)量不同時(shí)期DR患者黃斑區(qū)的脈絡(luò)膜厚度,發(fā)現(xiàn)與正常對(duì)照組比較,黃斑區(qū)脈絡(luò)膜厚度明顯變薄,得出結(jié)論:脈絡(luò)膜厚度降低可能導(dǎo)致組織缺氧進(jìn)而導(dǎo)致VEGF含量增加,最終引起血視網(wǎng)膜屏障破壞及黃斑水腫[23,24]。盡管結(jié)論有所不同,但均表明黃斑部脈絡(luò)膜厚度與DR的關(guān)系密切。
3.3 脈絡(luò)膜厚度與中心性滲出性脈絡(luò)膜視網(wǎng)膜病變 中心性滲出性脈絡(luò)膜視網(wǎng)膜病變又稱特發(fā)性脈絡(luò)膜新生血管(Idiopathic chroidal neovascularization,ICNV),主要損害50歲以下中青年人群的視力,發(fā)病機(jī)制不清,可能是與炎癥反應(yīng)有關(guān)的黃斑部滲出性病變,診斷時(shí)需除外老年性黃斑變性、高度近視、血管樣條紋病等引起的脈絡(luò)膜新生血管[25]。Spaide等研究[3]發(fā)現(xiàn)利用EDI SD-OCT可以測(cè)量脈絡(luò)膜厚度,并有助于更深入了解AMD,PCV,CSC等疾病的發(fā)病機(jī)制,由于ICNV的發(fā)病機(jī)制并不清楚,EDI SD-OCT通過(guò)測(cè)量黃斑部脈絡(luò)膜厚度,有助于了解其可能的發(fā)病機(jī)制。Cao等[26]選取20名單眼患病的ICNV患者,健康眼作為對(duì)照組進(jìn)行黃斑部脈絡(luò)膜厚度測(cè)量發(fā)現(xiàn),患眼的脈絡(luò)膜厚度明顯較健康眼變厚,并與ICNV患者ICGA造影的脈絡(luò)膜血管擴(kuò)張的高熒光表現(xiàn)相一致[27],而Chan等[28]發(fā)現(xiàn)經(jīng)過(guò)抗炎治療后,ICNV患者的脈絡(luò)膜血管的通透性明顯下降,因此,Cao等推測(cè)脈絡(luò)膜厚度增加可能與脈絡(luò)膜血管高通透性相關(guān),進(jìn)而推斷炎癥反應(yīng)可能在ICNV的發(fā)病機(jī)制中起到重要作用。
3.4 脈絡(luò)膜厚度與中心性漿液性脈絡(luò)膜視網(wǎng)膜病 中心性漿液性脈絡(luò)膜視網(wǎng)膜病,簡(jiǎn)稱中漿,是好發(fā)于男性的一種危害視力的自限性脈絡(luò)膜視網(wǎng)膜病變,一般發(fā)病3個(gè)月內(nèi)可自愈,但復(fù)發(fā)率較高,反復(fù)發(fā)作、病程遷延的患者視力可能受到損害[29,30]。有研究[31]發(fā)現(xiàn)中漿可能與A型人格、精神壓力大、類固醇激素使用相關(guān)。多項(xiàng)研究[32,33]顯示缺血和炎癥機(jī)制可能導(dǎo)致內(nèi)層脈絡(luò)膜血管通透性異常,進(jìn)而引起色素上皮脫離或微皺褶甚至撕裂,最終出現(xiàn)視網(wǎng)膜神經(jīng)上皮脫離的中漿典型表現(xiàn)。Brandl等[34]研究發(fā)現(xiàn),與正常對(duì)照組比較,中漿患者發(fā)病初期脈絡(luò)膜厚度明顯增厚,3個(gè)月后脈絡(luò)膜厚度明顯下降,但未達(dá)到正常水平,這也從組織學(xué)上證明了中漿的自限性。同時(shí),他們推測(cè)脈絡(luò)膜血管的高通透性及靜水壓增加是中漿的主要發(fā)病機(jī)制,而非單獨(dú)的RPE屏障受損。Pryds等[35]發(fā)現(xiàn),經(jīng)過(guò)PDT治療的中漿患者的脈絡(luò)膜厚度明顯變薄,且變薄的范圍遠(yuǎn)大于治療范圍,而且對(duì)側(cè)眼的脈絡(luò)膜厚度也較前變薄,推測(cè)中漿是原發(fā)于脈絡(luò)膜血管異常的疾病,視網(wǎng)膜色素上皮異常只是中漿的繼發(fā)表現(xiàn)。
3.5 脈絡(luò)膜厚度與葡萄膜炎 脈絡(luò)膜位于葡萄膜的后部,與多種后極部葡萄膜炎關(guān)系密切。原田-小柳病(Vogt-Koyanagi-Harada disease,VKH)是一種常累及雙眼的自身免疫性肉芽腫性葡萄膜炎,對(duì)激素治療敏感,但易復(fù)發(fā)[36]。既往研究[37]發(fā)現(xiàn)經(jīng)激素治療后,VKH患者的黃斑部脈絡(luò)膜厚度明顯降低。此外,有研究[38]指出,VKH復(fù)發(fā)患者未出現(xiàn)眼部炎癥表現(xiàn)時(shí),EDI SD-OCT就可以發(fā)現(xiàn)增加100μm以上的黃斑部脈絡(luò)膜厚度變化的亞臨床表現(xiàn)。
白塞氏病(Behcet‘s disease,BD)是一種累及眼、口、生殖器、皮膚等多器官的特發(fā)性血管閉塞性血管炎,常累及雙眼,眼部表現(xiàn)為非肉芽腫型葡萄膜炎[39]。韓國(guó)學(xué)者Kim等[40]針對(duì)30名BD患者的脈絡(luò)膜厚度研究指出,與靜止期比較,BD活動(dòng)期脈絡(luò)膜厚度明顯增加(P=0.004),靜止期患者的脈絡(luò)膜厚度也較正常健康者偏厚(P<0.0001)。與眼底熒光造影比較,脈絡(luò)膜厚度下降與視網(wǎng)膜血管滲漏明顯相關(guān)(P= 0.046)。Coskun等[41]通過(guò)比較伴或不伴有眼部葡萄膜炎的兩組BD患者的脈絡(luò)膜厚度發(fā)現(xiàn),伴有葡萄膜炎的BD患者的脈絡(luò)膜厚度較眼部無(wú)癥狀的患者更薄,推測(cè)可能BD患者由于炎癥反復(fù)發(fā)作,導(dǎo)致脈絡(luò)膜缺血缺氧及纖維化引起脈絡(luò)膜厚度薄變。分析以上研究可能因觀察疾病的時(shí)期不同而導(dǎo)致結(jié)論有所差異。以上研究提示黃斑部脈絡(luò)膜厚度對(duì)監(jiān)測(cè)葡萄膜炎的活動(dòng)性及指導(dǎo)治療有重要作用。
3.6 脈絡(luò)膜厚度與高度近視 高度近視是全球范圍內(nèi)導(dǎo)致視力損害的主要原因之一,在日本和中國(guó)尤為明顯[42,43]。高度近視患者易發(fā)生損害視力的并發(fā)癥主要是脈絡(luò)膜萎縮、脈絡(luò)膜新生血管、視網(wǎng)膜脫離、黃斑裂孔、黃斑劈裂、漆裂紋等。Takahashi等[44]研究發(fā)現(xiàn),眼軸長(zhǎng)度增加是導(dǎo)致高度近視并發(fā)癥的一個(gè)重要危險(xiǎn)因素,無(wú)論是發(fā)育期兒童還是眼球已發(fā)育完全的成人高度近視患者,眼軸進(jìn)行性延長(zhǎng)都會(huì)直接或間接地導(dǎo)致眼底的各種退行性病變,如視網(wǎng)膜脈絡(luò)膜萎縮、漆裂紋、黃斑劈裂、黃斑裂孔等。其中脈絡(luò)萎縮變薄是導(dǎo)致脈絡(luò)膜新生血管形成和中心視力損害的主要原因。傳統(tǒng)檢查方法如B超分辨率低、吲哚青綠血管造影無(wú)法觀察脈絡(luò)膜橫斷面情況,EDI SD-OCT技術(shù)可直接進(jìn)行脈絡(luò)膜掃描,脈絡(luò)膜橫斷面結(jié)構(gòu)顯示地更加清晰。既往研究[45,46]對(duì)成年高度近視眼及正常對(duì)照眼進(jìn)行測(cè)量發(fā)現(xiàn),成年人脈絡(luò)膜厚度在高度近視組與正常對(duì)照組均與年齡呈負(fù)相關(guān),高度近視組患者的脈絡(luò)膜厚度還與眼軸長(zhǎng)度呈負(fù)相關(guān),且厚度較正常對(duì)照組明顯變薄,且黃斑區(qū)平均脈絡(luò)膜厚度為115~142μm,眼軸長(zhǎng)度增加1mm,脈絡(luò)膜厚度減少約17.9~25.9μm。此外,有研究[47,48]發(fā)現(xiàn),經(jīng)PDT治療后的高度近視患者的脈絡(luò)膜視網(wǎng)膜萎縮明顯。通過(guò)EDI SD-OCT技術(shù)測(cè)量老年患者黃斑部脈絡(luò)膜厚度可能有助于預(yù)測(cè)高度近視患者各種并發(fā)癥發(fā)生的可能性。
綜上所述,EDI SD-OCT是一種重復(fù)性好、清晰度高、非侵入性的在體觀察脈絡(luò)膜橫斷面的重要技術(shù),其重要的臨床及科研價(jià)值已獲得肯定。脈絡(luò)膜異常與黃斑部多種疾病密切相關(guān),隨著研究的深入,人們對(duì)于脈絡(luò)膜與老年性黃斑疾病的關(guān)系有了更深入地了解,脈絡(luò)膜厚度分析對(duì)于老年性黃斑疾病的診斷、治療及預(yù)后觀察有重要的指導(dǎo)意義。但目前的研究還處于初級(jí)階段,脈絡(luò)膜在老年性黃斑病變的發(fā)病機(jī)制中的具體作用還有待于更進(jìn)一步深入的研究。
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The study development of relation between choroid thickness and macular diaseases
(SONG Shuang1,YU Xiaobing1,DAI Hong1,CHEN Qin1,SUN Liang2,ZHU Xiaoquan2,YUAN Huiping2,YANG Fan2,YANG Ze2.1.Ophthalmology department,Beijing hospital,Beijing 100730,China.2.Institute of geriatrics,Chinese ministry of health,Beijing hospital,Beijing 100730,China) Corresponding author:Yu Xiaoing.)
Macular diasease is a common disorder for some ocular fundus diaseses which damage vision function or reduce life quality of old patients even worse to lose sight.Choroid involve directly or indirectly in the physiological pathology of senility macular disease for rich blood vascular and high metabolism.Analyzing Choroid thickness is significant for diagnosis,treatment and prognosis of senility macular diseases.Here we review the study development of relation between choroid thickness and macular diaseases.
Choroid thickness,senility macular disease
10.3969/j.issn.1672-4860.2015.05.003
2015-7-15
北京醫(yī)院 1.眼科 2.衛(wèi)生部北京老年醫(yī)學(xué)研究所,衛(wèi)生部老年醫(yī)學(xué)重點(diǎn)實(shí)驗(yàn)室 100730
國(guó)家自然科學(xué)基金(81061120527,81370445,81472408,81400790);衛(wèi)生部公益性研究基金(201302008);國(guó)家科技部十二五支撐計(jì)劃(2012BAI10B01);北京市科技新星計(jì)劃(Z121107002512058)
宋爽,醫(yī)學(xué)博士,住院醫(yī)師,研究方向眼底病學(xué)。
※通訊作者:喻曉兵,醫(yī)學(xué)博士,主任醫(yī)師,碩士研究生導(dǎo)師,從事多年眼底病相關(guān)的診斷與治療工作,技術(shù)精湛,在干部保健工作方面有著豐富的臨床經(jīng)驗(yàn)。