戴琰琰，蔣正軒，廖榮豐

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康柏西普治療滲出性老年性黃斑變性療效觀察

戴琰琰1，2，蔣正軒1，廖榮豐1

收集經(jīng)熒光素鈉眼底血管造影(FFA)、相干光斷層掃描(OCT)檢查確診為滲出性老年性黃斑變性的25只眼為觀察對(duì)象，所有患眼按3+PRN方案，接受10 mg/ml康柏西普0.05 ml玻璃體腔注射，行注射前后自身對(duì)照研究。采用糖尿病視網(wǎng)膜病變?cè)缙谥委熝芯恳暳Ρ頇z查最佳矯正視力(BCVA)，OCT檢查測(cè)量黃斑中心凹視網(wǎng)膜厚度(CRT)。對(duì)比分析治療前后患眼BCVA、CRT的變化,同時(shí)觀察隨訪期間眼部與全身不良反應(yīng)情況。治療后1、2、3個(gè)月及末次隨訪時(shí)患眼平均BCVA較治療前提高，差異有統(tǒng)計(jì)學(xué)意義(t=4.27、6.43、7.75、7.36，P<0.05)；平均CRT較治療前降低，差異有統(tǒng)計(jì)學(xué)意義(t=11.97、10.49、10.02、8.67，P<0.05)。隨訪期間未見與治療相關(guān)的嚴(yán)重眼部并發(fā)癥及全身不良反應(yīng)。

玻璃體腔注射；滲出性老年性黃斑變性；康柏西普

年齡相關(guān)性黃斑變性(age-related macular degeneration，AMD)是眼科常見的致盲眼病之一，尤其是濕性的AMD致盲率較高。濕性AMD的病理特征是黃斑區(qū)出現(xiàn)脈絡(luò)膜新生血管(choroidal neovascularization，CNV)，常導(dǎo)致黃斑區(qū)出血、滲出、水腫、視網(wǎng)膜色素上皮脫離，晚期黃斑區(qū)廣泛瘢痕化。因此患者視力遭到嚴(yán)重?fù)p害[1-4]。目前對(duì)濕性AMD的治療主要是使用抗血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor，VEGF)類藥物來抑制新生血管生長(zhǎng)。該研究采用玻璃體腔注射康柏西普對(duì)濕性AMD患者進(jìn)行治療，現(xiàn)做如下總結(jié)。

1 材料與方法

1.1 病例資料 收集2014年7月～2015年7月在安徽醫(yī)科大學(xué)第一附屬醫(yī)院就診并被確診為濕性AMD的25只患眼作為研究對(duì)象。所有患者按3+PRN方案(前3個(gè)月每月注射1次，后期按需注射)接受10 mg/ml康柏西普0.05 ml玻璃體腔注射且資料完整，其中男13眼，女12眼，年齡50～70(56.2±3.3)歲。

1.2 方法 所有患者術(shù)前進(jìn)行最佳矯正視力(best corrected visual acuity，BCVA)、裂隙燈、Amsler方格、直間接檢眼鏡，眼底熒光血管造影(fundus fluorescein angiography,FFA)、光學(xué)相干層析成像 (optical coherence tomography,OCT)等檢查。BCVA檢查使用糖尿病視網(wǎng)膜病變?cè)缙谥委熝芯恳暳Ρ磉M(jìn)行；眼壓測(cè)量使用日本NIDEK公司非接觸眼壓計(jì)；FFA檢查使用德國(guó)海德堡共焦激光眼底造影儀；OCT檢查使用TOPCON公司3DOCT-1000。FFA檢查顯示，所有患眼黃斑區(qū)CNV病灶滲漏明顯(圖1A為代表)；OCT檢查顯示，所有患眼黃斑區(qū)視網(wǎng)膜水腫(圖1B為代表)；所有患眼符合濕性AMD的臨床診斷標(biāo)準(zhǔn)并參照國(guó)內(nèi)外相關(guān)文獻(xiàn)[5-8]設(shè)定納入標(biāo)準(zhǔn)及重復(fù)治療指征。治療前3 d，0.5%左氧氟沙星滴眼液，4次/d，點(diǎn)術(shù)眼。手術(shù)室內(nèi)按內(nèi)眼手術(shù)要求常規(guī)消毒鋪巾，整個(gè)玻璃體腔注射過程嚴(yán)格按照朗沐注射液使用說明書規(guī)定流程操作。注射完畢給予妥布霉素地塞米松眼膏涂眼并包扎術(shù)眼，2 h后打開術(shù)眼敷料行裂隙燈檢查眼前節(jié)情況，并指測(cè)眼壓，無異常者術(shù)后當(dāng)天予以0.5%左氧氟沙星滴眼液滴眼，4次/d，妥布霉素地塞米松滴眼液滴眼,3次/d及2%鹽酸卡替洛爾滴眼液滴眼，2次/d。

圖1 注射藥物前眼底熒光素鈉造影及OCT表現(xiàn)

1.3 隨訪及觀察指標(biāo) 治療后隨訪4～9(4.25±0.79)個(gè)月。注射次日，用裂隙燈行眼前節(jié)檢查，非接觸式眼壓計(jì)測(cè)眼壓，眼壓<21 mmHg和少量球結(jié)膜下出血者，不予處理；角膜上皮損傷者，用左氧氟沙星眼膏包眼；眼壓>21 mmHg者，予以2%鹽酸卡替洛爾滴眼液滴眼2次/d，3 d后復(fù)查。以后每個(gè)月行BCVA、眼壓、裂隙燈，直、間接檢眼鏡、Amsler方格、OCT、FFA檢查。下圖2為圖1患者治療1個(gè)月后圖像，圖2A為與圖1A患者同期FFA示黃斑區(qū)CNV病灶基本無滲漏；圖2B示黃斑區(qū)水腫消退CNV病灶縮小、纖維化。

圖2 注射藥物1個(gè)月后眼底熒光素鈉造影及OCT表現(xiàn)

2 結(jié)果

治療隨訪期間3例患者出現(xiàn)一過性眼壓升高，5例球結(jié)膜下出血，2例角膜上皮點(diǎn)狀浸潤(rùn)，所有患者CRT較治療前降低，5例患者BCVA出現(xiàn)波動(dòng)，具體數(shù)據(jù)見表1，未見眼部及全身嚴(yán)重不良反應(yīng)。

表1 康柏西普注射前后BCVA及CRT的比較

3 討論

我國(guó)自主研發(fā)的新型抗VEGF的融合蛋白是由VEGF受體1、VEGF受體2和人免疫球蛋白IgG-1部分片段融合而成，能結(jié)合VEGF-A所有亞型、VEGF-B及胎盤生長(zhǎng)因子，具有多靶點(diǎn)、親和力強(qiáng)、作用時(shí)間長(zhǎng)等特點(diǎn)[5-6]。雖然本研究采用開放的無對(duì)照的觀察，但結(jié)果顯示有20%的患者術(shù)后視力顯著提高，60%視力提高，20%患者隨訪期間視力出現(xiàn)小幅度波動(dòng)。所有患者隨訪期間行Amsler方格檢查時(shí)訴視物清晰度增加、變形好轉(zhuǎn)，部分患者中心暗點(diǎn)及旁中心暗點(diǎn)消失；OCT顯示所有患者黃斑中心凹厚度較術(shù)前降低，這說明此治療從解剖結(jié)構(gòu)上為患者主觀癥狀的改善可以提供了理論支持。本研究顯示視力顯著提高的患者多為自覺視力下降、視物變形不超過1周即到醫(yī)院就診，F(xiàn)FA顯示滲漏明顯，CNV面積較小且不位于黃斑中心凹下；視力提高不明顯的患者多為自覺視力下降超過1個(gè)月就診，F(xiàn)FA顯示滲漏明顯，CNV面積較大且位于黃斑中心凹下，這或許提示治療時(shí)機(jī)、CNV的大小、位置均對(duì)預(yù)后產(chǎn)生影響：早期治療，CNV相對(duì)較小以及位置偏黃斑中心凹術(shù)后視力提高越明顯。本研究亦表明若初次注射患者對(duì)本藥物的反應(yīng)敏感性高，在后期的治療中該患者始終保持相對(duì)良好的敏感性，尚未顯示與其他抗VEGF類藥物類似的不應(yīng)答現(xiàn)象，這可能與康柏西普具有多靶點(diǎn)、親和力強(qiáng)、作用時(shí)間長(zhǎng)的特點(diǎn)有關(guān)，也不排除由于本研究樣本量少且隨訪時(shí)間較短而導(dǎo)致的誤差。

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Observation of Conbercept treatment on wet age-related macular degeneration

Dai Yanyan1,2，Jiang Zhengxuan1，Liao Rongfeng1

(1DeptofOphthalmology,TheFirstAffiliatedHospitalofAnhuiMedicalUniversity,Hefei230022;2DeptofOphthalmology,AnhuiNO.2ProvincePeople’sHospital,Hefei200041)

Twenty-five eyes which were diagnosed with exudative macular degeneration (eAMD) by fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) were enrolled in the study. All affected eyes were injected by conbercept, following a 3+PRN schedule intravenously and treated with 0.05 ml (10 mg/ml), was a self-control study before and after injection. Using the early treatment of diabetic retinopathy study (ETDRS) examine the best corrected visual acuity (BCVA) and OCT examine the central retina thickness (CRT). The paired t-test was used to compare the BCVA, CRT before and after treatment. Simultaneously, the occurrences of ocular and systemic adverse reactions were observed during follow-up duration. During the 1，2，3 months after treatment and the latest follow up ,the mean BCVA were all improved with significant difference (t=4.27，6.43，7.75，7.36,P<0.05). The mean CRT were significantly decreased with significant difference(t=11.97，10.49，10.02，8.67,P<0.05). No systemic adverse reactions and treatment-related serious ocular complications were found during the follow-up duration.

intravitreal; wet macular degeneration; conbercept

安徽高校省級(jí)自然科學(xué)研究項(xiàng)目(編號(hào)：KJ2013A147)

1安徽醫(yī)科大學(xué)第一附屬醫(yī)院眼科，合肥 2300222安徽省第二人民醫(yī)院眼一科，合肥 200041

戴琰琰，女，碩士研究生； 廖榮豐，男，教授，主任醫(yī)師，碩士生導(dǎo)師，責(zé)任作者，E-mail：liaorfayfy@126.com

時(shí)間：2016-10-12 13:23:00

http://www.cnki.net/kcms/detail/34.1065.R.20161012.1323.037.html

R 774.5

A

1000-1492(2016)11-1707-03

10.19405/j.cnki.issn1000-1492.2016.11.037

2016-07-21接收