光学相干断层扫描血管成像对玻璃体腔注射雷珠单抗治疗湿性年龄相关性黄斑变性的随访观察
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摘要
目的利用光学相干断层扫描血管成像(OCTA)观察雷珠单抗玻璃体腔注射3次+必要时(3+PRN)方案治疗湿性年龄相关性黄斑变性(AMD)的图像特征。方法选取2016年9月至2017年5月经荧光素眼底血管造影(FFA)、吲哚菁绿血管造影(ICGA)检查确诊且未予治疗的湿性AMD患者8例8只眼,按照3+PRN治疗方案给予玻璃体腔注射雷珠单抗(0.5 mg/0.05 ml)治疗,采用OCTA 6 mm×6 mm范围模式扫描黄斑区视网膜,在患者治疗前,治疗后1、3、6个月进行规律的门诊随访,记录患者最小分辨角对数(logMAR)矫正视力、脉络膜新生血管(CNV)分型、CNV形态特征及变化、黄斑中心凹视网膜厚度(CRT)、黄斑区视网膜外层血流密度(ORVD)及脉络膜毛细血管层血流密度(CCVD)。结果男性4例4只眼,女性4例4只眼,平均年龄(70.9±10.6)岁;3只眼为Ⅰ型CNV,5只眼为Ⅱ型CNV。治疗前,治疗后1、3、6个月最佳矫正视力(BCVA)分别为0.55(0.33,0.87)、0.35(0.24,0.84)、0.35(0.22,0.58)、0.26(0.10,0.58)logMAR,各组间差异均无统计学意义(P均>0.05);CRT分别为(271.88±91.95)、(204.00±45.78)、(196.00±31.14)、(219.25±71.32)μm,其中,治疗3个月与治疗前差异有统计学意义(t=2.211,P=0.044);ORVD分别为(41.38±2.77)%、(41.73±3.60)%、(42.53±1.95)%、(41.40±2.33)%,各组间差异均无统计学意义(P均>0.05);CCVD分别为(64.38±2.24)%、(64.96±1.39)%、(64.16±1.39)%、(64.63±1.86)%,各组间差异也均无统计学意义(P均>0.05)。相关性分析结果显示,BCVA与CRT(P=0.009,RR=0.457)和CCVD(P=0.001,RR=0.574)显著相关,与ORVD(P=0.093,RR=0.302)不相关。治疗前CNV形态特征,2只眼为团状,2只眼为线条样,2只眼为纠缠错乱状,1只眼为椭圆环形,1只眼为碎片样。治疗1个月,7只眼CNV形态趋于正常化,表现为CNV最大直径减小、断裂/破碎、周边毛细血管丢失、数量和密度下降、所在区域最大横截面积减小;1只眼CNV形态较前恶化,表现为CNV吻合成环、密度增加、最大血管直径增加。治疗3个月,7只眼CNV形态趋于正常化,1只眼较前无明显变化。治疗6个月,5只眼CNV趋于正常化,3只眼恶化。随访中未发现眼内感染或玻璃体内注射的其他并发症。结论利用OCTA技术观察CNV特征能够评估湿性AMD患者接受雷珠单抗治疗的疗效,可为湿性AMD患者的治疗与随访提供指导。
Objective To observe the imaging features of optical coherence tomography angiography(OCTA)in eyes with wet age-related macular degeneration(wAMD)after treatment with 3+pro re nata(3+PRN)of intravitreal anti-Ranibizumab.Methods This study included 8 treatment-naive eyes with wAMD diagnosed by fluorescein fundus angiography(FFA)and indocyanine green angiography(ICGA)from September 2016 to May 2017.All the patients were treated with 3+PRN of intravitreal anti-Ranibizumab(0.5 mg/0.05 ml).We performed OCTA with 6 mm×6 mm scans at baseline and 1,3,and 6 months after treatment.We analyzed best corrected visual acuity(BCVA)(logMAR),type of choroidal neovascular(CNV),and morphological features and changes of CNV,central retinal thickness(CRT),outer retina vessel density(ORVD),and choroidal capillary vessel density(CCVD).Results A total of 8 eyes were examined in 8 patients[4 males and 4 females with a mean age of(70.9±10.6)years of age].Three eyes had type Ⅰ CNV and 5 eyes had type Ⅱ CNV.At baseline,month 1,month 3,and month 6,BCVA was 0.55(0.33,0.87),0.35(0.24,0.84),0.35(0.22,0.58),and 0.26(0.10,0.58)logMAR,respectively(all P>0.05).CRT was(271.88±91.95),(204.00±45.78),(196.00±31.14),and(219.25±71.32)μm,respectively,and there was a statistical significance between CRT at baseline and CRT at month 3(t=2.211,P=0.044).ORVD was(41.38±2.77)%,(41.73±3.60)%,(42.53±1.95)%,and(41.40±2.33)%,respectively(all P>0.05).CCVD was(64.38±2.24)%,(64.96±1.39)%,(64.16±1.39)%,and(64.63±1.86)%,respectively(all P>0.05).Correlation analysis showed BCVA was significantly correlated with both CRT(P=0.009, RR=0.457)and CCVD(P=0.001,RR=0.574),but not with ORVD(P=0.093,RR=0.302).The morphological features at baseline showed that 2 eyes were lump-like,2 eyes were line-like,2 eyes were tangles,1 eye was elliptical ring-like,and 1 eye was fragment.At month 1,the morphologies were improved in 7 eyes,including the CNV showed decreased maximum diameter,rupture/fragment,loss of peripheral capillaries,decreased numbers and density,and reduced maximum cross-sectional area;the condition became worse in 1 eye,including the CNV showed ring formation,increased density,and increased maximum diameter.At month 3,the morphologied of 7 eyes were improved,while no obvious change was seen in 1 eye.At month 6,the CNV became normalized in 5 eyes but worsened in 3 eyes.No intraocular infection or other intravitreal injection-related complication was observed during the follow-up.Conclusion Observing CNV characteristics using OCTA technology can be used to evaluate the efficacy of Ranibizumab in patients with wAMD and guide the treatment and follow-up of wAMD patients.
Objective To observe the imaging features of optical coherence tomography angiography(OCTA)in eyes with wet age-related macular degeneration(wAMD)after treatment with 3+pro re nata(3+PRN)of intravitreal anti-Ranibizumab.Methods This study included 8 treatment-naive eyes with wAMD diagnosed by fluorescein fundus angiography(FFA)and indocyanine green angiography(ICGA)from September 2016 to May 2017.All the patients were treated with 3+PRN of intravitreal anti-Ranibizumab(0.5 mg/0.05 ml).We performed OCTA with 6 mm×6 mm scans at baseline and 1,3,and 6 months after treatment.We analyzed best corrected visual acuity(BCVA)(logMAR),type of choroidal neovascular(CNV),and morphological features and changes of CNV,central retinal thickness(CRT),outer retina vessel density(ORVD),and choroidal capillary vessel density(CCVD).Results A total of 8 eyes were examined in 8 patients[4 males and 4 females with a mean age of(70.9±10.6)years of age].Three eyes had type Ⅰ CNV and 5 eyes had type Ⅱ CNV.At baseline,month 1,month 3,and month 6,BCVA was 0.55(0.33,0.87),0.35(0.24,0.84),0.35(0.22,0.58),and 0.26(0.10,0.58)logMAR,respectively(all P>0.05).CRT was(271.88±91.95),(204.00±45.78),(196.00±31.14),and(219.25±71.32)μm,respectively,and there was a statistical significance between CRT at baseline and CRT at month 3(t=2.211,P=0.044).ORVD was(41.38±2.77)%,(41.73±3.60)%,(42.53±1.95)%,and(41.40±2.33)%,respectively(all P>0.05).CCVD was(64.38±2.24)%,(64.96±1.39)%,(64.16±1.39)%,and(64.63±1.86)%,respectively(all P>0.05).Correlation analysis showed BCVA was significantly correlated with both CRT(P=0.009, RR=0.457)and CCVD(P=0.001,RR=0.574),but not with ORVD(P=0.093,RR=0.302).The morphological features at baseline showed that 2 eyes were lump-like,2 eyes were line-like,2 eyes were tangles,1 eye was elliptical ring-like,and 1 eye was fragment.At month 1,the morphologies were improved in 7 eyes,including the CNV showed decreased maximum diameter,rupture/fragment,loss of peripheral capillaries,decreased numbers and density,and reduced maximum cross-sectional area;the condition became worse in 1 eye,including the CNV showed ring formation,increased density,and increased maximum diameter.At month 3,the morphologied of 7 eyes were improved,while no obvious change was seen in 1 eye.At month 6,the CNV became normalized in 5 eyes but worsened in 3 eyes.No intraocular infection or other intravitreal injection-related complication was observed during the follow-up.Conclusion Observing CNV characteristics using OCTA technology can be used to evaluate the efficacy of Ranibizumab in patients with wAMD and guide the treatment and follow-up of wAMD patients.
引文
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[13] Carpineto P,Mastropasqua R,Marchini G,et al.Reproducibility and repeatability of foveal avascular zone measurements in healthy subjects by optical coherence tomography angiography[J].Br J Ophthalmol,2016,100(5):671- 676.DOI:10.1136/bjophthalmol- 2015- 307330.
[14] Gao SS,Jia Y,Zhang M,et al.Optical coherence tomography angiography[J].Invest Ophthalmol Vis Sci,2016,57(9):T27-T36.DOI:10.1167/iovs.15- 19043.
[15] Lim LS,Mitchell P,Seddon JM,et al.Age-related macular degeneration[J].Lancet,2012,379(9827):1728- 1738.DOI:10.1016/S0140- 6736(12)60282- 7.
[16] Do DV,Gower EW,Cassard SD,et al.Detection of new-onset choroidal neovascularization using optical coherence tomography:the AMD DOC Study[J].Ophthalmology,2012,119(4):771- 778.DOI:10.1016/j.ophtha.2011.10.019.
[17] Reis GM,Grigg J,Chua B,et al.Incidence of intraocular pressure elevation following intravitreal ranibizumab(lucentis)for age-related macular degeneration[J].J Curr Glaucoma Pract,2017,11(1):3- 7.DOI:10.5005/jp-journals- 10008- 1213.
[18] Johnston RL,Carius HJ,Skelly A,et al.A retrospective study of ranibizumab treatment regimens for neovascular age-related macular degeneration(nAMD)in Australia and the United Kingdom[J].Adv Ther,2017,34(3):703- 712.DOI:10.1007/s12325- 017- 0483- 1.
[19] Ferris FR,Wilkinson CP,Bird A,et al.Clinical classification of age-related macular degeneration[J].Ophthalmology,2013,120(4):844- 851.DOI:10.1016/j.ophtha.2012.10.036.
[20] Ueta T,Noda Y,Toyama T,et al.Systemic vascular safety of ranibizumab for age-related macular degeneration:systematic review and meta-analysis of randomized trials[J].Ophthalmology,2014,121(11):2193- 2203.DOI:10.1016/j.ophtha.2014.05.022.
[21] de Carlo TE,Bonini FM,Chin AT,et al.Spectral-domain optical coherence tomography angiography of choroidal neovascularization[J].Ophthalmology,2015,122(6):1228- 1238.DOI:10.1016/j.ophtha.2015.01.029.
[22] Coscas GJ,Lupidi M,Coscas F,et al.Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration:a new diagnostic challenge[J].Retina,2015,35(11):2219- 2228.DOI:10.1097/IAE.0000000000000766.
[23] Moult E,Choi W,Waheed NK,et al.Ultrahigh-speed swept-source OCT angiography in exudative AMD[J].Ophthalmic Surg Lasers Imaging Retina,2014,45(6):496- 505.DOI:10.3928/23258160- 20141118- 03.
[24] Coscas G,Lupidi M,Coscas F,et al.Optical coherence tomography angiography during follow-up:qualitative and quantitative analysis of mixed type Ⅰ and Ⅱ choroidal neovascularization after vascular endothelial growth factor trap therapy[J].Ophthalmic Res,2015,54(2):57- 63.DOI:10.1159/000433547.
[25] Muakkassa NW,Chin AT,de Carlo T,et al.Characterizing the effect of anti-vascular endothelial growth factor therapy on treatmentnaive choroidal neovascularization using optical coherence tomography angiography[J].Retina,2015,35(11):2252- 2259.DOI:10.1097/IAE.0000000000000836.
[26] Coscas GJ,Lupidi M,Coscas F,et al.Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration:a new diagnostic challenge[J].Retina,2015,35(11):2219- 2228.DOI:10.1097/IAE.0000000000000766.
[27] Kuehlewein L,Bansal M,Lenis TL,et al.Optical coherence tomography angiography of type 1 neovascularization in age-related macular degeneration[J].Am J Ophthalmol,2015,160(4):739- 748.DOI:10.1016/j.ajo.2015.06.030.
[28] Xu D,Davila JP,Rahimi M,et al.Long-term progression of type 1 neovascularization in age-related macular degeneration using optical coherence tomography angiography[J].Am J Ophthalmol,2018,187:10- 20.DOI:10.1016/j.ajo.2017.12.005.
[29] 杨景元.光相干断层扫描血管成像在眼底疾病诊断研究中的应用[J].中华实验眼科杂志,2017,35(10):944- 948.DOI:10.3760/cma.j.issn.2095- 0160.2017.10.020.
[30] Cole ED,Ferrara D,Novais EA,et al.Clinical trial endpoints for optical coherence tomography angiography in neovascular age-related macular degeneration [J].Retina,2016,36(Suppl 1):S83-S92.DOI:10.1097/IAE.0000000000001338.
[31] Miere A,Oubraham H,Amoroso F,et al.Optical coherence tomography angiography to distinguish changes of choroidal neovascularization after anti-VEGF therapy:monthly loading dose versus pro re nata regimen[J].J Ophthalmol,2018,2018:3751702.DOI:10.1155/2018/3751702.
[2] Pascolini D,Mariotti SP.Global estimates of visual impairment:2010[J].Br J Ophthalmol,2012,96(5):614- 618.DOI:10.1136/bjophthalmol- 2011- 300539.
[3] Song P,Du Y,Chan KY,et al.The national and subnational prevalence and burden of age-related macular degeneration in China[J].J Glob Health,2017,7(2):1- 16.DOI:10.7189/jogh.07.020703.
[4] Nagiel A,Sarraf D,Sadda SR,et al.Type 3 neovascularization:evolution,association with pigment epithelial detachment,and treatment response as revealed by spectral domain optical coherence tomography[J].Retina,2015,35(4):638- 647.DOI:10.1097/IAE.0000000000000488.
[5] Kuehlewein L,Dansingani KK,de Carlo TE,et al.Optical coherence tomography angiography of type 3 neovascularization secondary to age-related macular degeneration[J].Retina,2015,35(11):2229- 2235.DOI:10.1097/IAE.0000000000000835.
[6] Phasukkijwatana N,Tan A,Chen X,et al.Optical coherence tomography angiography of type 3 neovascularisation in age-related macular degeneration after antiangiogenic therapy[J].Br J Ophthalmol,2017,101(5):597- 602.DOI:10.1136/bjophthalmol- 2016- 308815.
[7] Jung JJ,Chen CY,Mrejen S,et al.The incidence of neovascular subtypes in newly diagnosed neovascular age-related macular degeneration[J].Am J Ophthalmol,2014,158(4):769- 779.DOI:10.1016/j.ajo.2014.07.006.
[8] Engelbert M,Zweifel SA,Freund KB.Long-term follow-up for type 1(subretinal pigment epithelium)neovascularization using a modified “treat and extend” dosing regimen of intravitreal antivascular endothelial growth factor therapy[J].Retina,2010,30(9):1368- 1375.DOI:10.1097/IAE.0b013e3181d50cbf.
[9] Ambati J,Ambati BK,Yoo SH,et al.Age-related macular degeneration:etiology,pathogenesis,and therapeutic strategies[J].Surv Ophthalmol,2003,48(3):257- 293.DOI:10.1016/s0039- 6257(03)00030- 4.
[10] Schmidt-Erfurth U,Chong V,Loewenstein A,et al.Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists(EURETINA)[J].Br J Ophthalmol,2014,98(9):1144- 1167.DOI:10.1136/bjophthalmol- 2014- 305702.
[11] Kaiser PK.Emerging therapies for neovascular age-related macular degeneration:drugs in the pipeline[J].Ophthalmology,2013,120(5 Suppl):S11-S15.DOI:10.1016/j.ophtha.2013.01.061.
[12] Wang RK,An L,Francis P,et al.Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography[J].Opt Lett,2010,35(9):1467- 1469.DOI:10.1364/OL.35.001467.
[13] Carpineto P,Mastropasqua R,Marchini G,et al.Reproducibility and repeatability of foveal avascular zone measurements in healthy subjects by optical coherence tomography angiography[J].Br J Ophthalmol,2016,100(5):671- 676.DOI:10.1136/bjophthalmol- 2015- 307330.
[14] Gao SS,Jia Y,Zhang M,et al.Optical coherence tomography angiography[J].Invest Ophthalmol Vis Sci,2016,57(9):T27-T36.DOI:10.1167/iovs.15- 19043.
[15] Lim LS,Mitchell P,Seddon JM,et al.Age-related macular degeneration[J].Lancet,2012,379(9827):1728- 1738.DOI:10.1016/S0140- 6736(12)60282- 7.
[16] Do DV,Gower EW,Cassard SD,et al.Detection of new-onset choroidal neovascularization using optical coherence tomography:the AMD DOC Study[J].Ophthalmology,2012,119(4):771- 778.DOI:10.1016/j.ophtha.2011.10.019.
[17] Reis GM,Grigg J,Chua B,et al.Incidence of intraocular pressure elevation following intravitreal ranibizumab(lucentis)for age-related macular degeneration[J].J Curr Glaucoma Pract,2017,11(1):3- 7.DOI:10.5005/jp-journals- 10008- 1213.
[18] Johnston RL,Carius HJ,Skelly A,et al.A retrospective study of ranibizumab treatment regimens for neovascular age-related macular degeneration(nAMD)in Australia and the United Kingdom[J].Adv Ther,2017,34(3):703- 712.DOI:10.1007/s12325- 017- 0483- 1.
[19] Ferris FR,Wilkinson CP,Bird A,et al.Clinical classification of age-related macular degeneration[J].Ophthalmology,2013,120(4):844- 851.DOI:10.1016/j.ophtha.2012.10.036.
[20] Ueta T,Noda Y,Toyama T,et al.Systemic vascular safety of ranibizumab for age-related macular degeneration:systematic review and meta-analysis of randomized trials[J].Ophthalmology,2014,121(11):2193- 2203.DOI:10.1016/j.ophtha.2014.05.022.
[21] de Carlo TE,Bonini FM,Chin AT,et al.Spectral-domain optical coherence tomography angiography of choroidal neovascularization[J].Ophthalmology,2015,122(6):1228- 1238.DOI:10.1016/j.ophtha.2015.01.029.
[22] Coscas GJ,Lupidi M,Coscas F,et al.Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration:a new diagnostic challenge[J].Retina,2015,35(11):2219- 2228.DOI:10.1097/IAE.0000000000000766.
[23] Moult E,Choi W,Waheed NK,et al.Ultrahigh-speed swept-source OCT angiography in exudative AMD[J].Ophthalmic Surg Lasers Imaging Retina,2014,45(6):496- 505.DOI:10.3928/23258160- 20141118- 03.
[24] Coscas G,Lupidi M,Coscas F,et al.Optical coherence tomography angiography during follow-up:qualitative and quantitative analysis of mixed type Ⅰ and Ⅱ choroidal neovascularization after vascular endothelial growth factor trap therapy[J].Ophthalmic Res,2015,54(2):57- 63.DOI:10.1159/000433547.
[25] Muakkassa NW,Chin AT,de Carlo T,et al.Characterizing the effect of anti-vascular endothelial growth factor therapy on treatmentnaive choroidal neovascularization using optical coherence tomography angiography[J].Retina,2015,35(11):2252- 2259.DOI:10.1097/IAE.0000000000000836.
[26] Coscas GJ,Lupidi M,Coscas F,et al.Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration:a new diagnostic challenge[J].Retina,2015,35(11):2219- 2228.DOI:10.1097/IAE.0000000000000766.
[27] Kuehlewein L,Bansal M,Lenis TL,et al.Optical coherence tomography angiography of type 1 neovascularization in age-related macular degeneration[J].Am J Ophthalmol,2015,160(4):739- 748.DOI:10.1016/j.ajo.2015.06.030.
[28] Xu D,Davila JP,Rahimi M,et al.Long-term progression of type 1 neovascularization in age-related macular degeneration using optical coherence tomography angiography[J].Am J Ophthalmol,2018,187:10- 20.DOI:10.1016/j.ajo.2017.12.005.
[29] 杨景元.光相干断层扫描血管成像在眼底疾病诊断研究中的应用[J].中华实验眼科杂志,2017,35(10):944- 948.DOI:10.3760/cma.j.issn.2095- 0160.2017.10.020.
[30] Cole ED,Ferrara D,Novais EA,et al.Clinical trial endpoints for optical coherence tomography angiography in neovascular age-related macular degeneration [J].Retina,2016,36(Suppl 1):S83-S92.DOI:10.1097/IAE.0000000000001338.
[31] Miere A,Oubraham H,Amoroso F,et al.Optical coherence tomography angiography to distinguish changes of choroidal neovascularization after anti-VEGF therapy:monthly loading dose versus pro re nata regimen[J].J Ophthalmol,2018,2018:3751702.DOI:10.1155/2018/3751702.