全氟萘烷液在眼内应用的临床及实验研究
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摘要
目的：全氟化碳液(Perflurocarbon liquids，PFCLs)是玻璃体视网膜手术(Vitreoretinal Surgery，VRS)中重要的玻璃体替代物，全氟萘烷(Perfluorodecalin，PFDL C_(10)F_(18))是PFCLs中的一种，为高碳液态氟化物，具有比重高、黏度低、无色透明、沸点高及很强的氧结合力等特点。可浮起玻璃体内晶状体及异物，机械压迫及固定视网膜，使之展平，减少术中损伤，很适合作为VRS中暂时性“液态使用材料”，现已广泛在眼科临床中应用。关于PFDL是否对角膜、视网膜等结构和功能有损害，目前的研究多限于临床观察，很多问题尚不清楚。本研究的实验部份采用眼内注射PFDL的疗法，从兔角膜、房角、视网膜及视神经的组织病理学和超微结构的改变，及通过角膜内皮镜、视网膜电流图(electroretinogram，ERG)和视觉诱发电位(visual evoked potential，VEP)等检查手段探讨PFDL是否会产生毒性作用，及对产生的毒性作用与PFDL的制量和存留时间的关系、机理及防治方法等作系统研究。本研究的临床部份观察在VRS中应用PFDL治疗复杂性视网膜脱离(retinal detachment，RD)、增生性糖尿病性视网膜病变(Proliferative diabetic retinopathy，PDR)、玻璃体积血、处理VRS中并发症及硅油下RD等的有效作用，判断PFDL残留可否引起明显眼部损害及眼部感染，并提出预防PFDL残留的方法。
方法：本研究采用动物实验和临床的方法，探讨PFDL对眼组织的损害作用。
1．全氟萘烷液在眼内应用的实验研究
选择健康家兔32只，随机分为前房及玻璃体腔两组，填充不同剂量的PFDL，在填充术后6h、24h、72h、7d、1mon、2mon分别进行以下实验观察：(1)．采用裂隙灯显微镜、间接检眼镜观察角膜透明度、虹膜有无新生血
天津医科大学硕士研究生学{方沦之
管、PFDL的性状、视网膜有无裂孔及脱离等改变。(2)采用ERG及VEP检改
视网膜及视神经的功能改变。(3)采用角膜内皮显微镜观察角!!莫内皮锁‘:i!:拈
况。(4)采用超声生物显微(ultrasound biomicroscopy，UBM)检查眼前、、的‘，父，Jk.、
(5)采用电镜及光镜检查，对角膜、前房角、视网膜及视神经等组织标本进行
超微结构砂!;究。，
2.全氟蔡烷液在眼内应用的临床研究
总结研究在VRS中应用PFDL治疗临床病例245例245只眼，上鲜，!，义杂
性RD 1 75例1 75只眼、PDRZI例21只眼、其它原因的玻璃体积!{{1.27例27三七
眼、急性视I冈膜坏死(aeute retinal neerosis，从N)2例2只眼、眼内炎3例3三乏
眼、Coats病1例1只眼、陈旧性脉络膜大出血1例1只眼、处理VRS后井发
症6例6只眼、硅油下RDg例9只眼。术中采用玻璃体切割，!摸剥离，PFOL
使用，眼内i放光.气液交换，惰性气体及硅油眼内填充等)’J法，、探讨在VRS
中应用PFDL防止眼内存留的方法，即在复杂性RD的VRS中为防比pFOL残
留和PFDL进入视网膜下，对黄斑裂孔或后极部裂孔患者采用“之一毛液交换后.汽
换PFDL法”，先行气液交换，铺平视网膜，再注入PFDL:对卜.人裂孔性
RD采川“PFDL联合部份气液交换法”，少七注入部份 PFDL，}I少亏J几部分‘七液交
换，作硅油或气体与PFDL交换;对3600视网膜切开患者采川“逐步使川
PFDL法”，先切开部分僵硬的视网膜，注入部份PFDL，逐步切川川心子卿可
膜，剥离增殖膜及牵拉组织，不断注入PFDL，}访l卜视网膜移位和PFDL进入视
网膜下。采用裂隙灯显微镜、间接检眼镜等方法观察术中使用PFDL的病例角
膜、虹膜、视网膜等改变，及随访观察PFDL残留病例。
结果:
1前房内填充0.3~o.6ml及玻璃体腔内填充0.5~3m!PFOL术后第
lmon，角膜内皮细胞密度非常显著下降(r=11471，尸<0.001)，平均乡11胞一!z一积
非常显著下降(t=12.393，p<0.001)及六角形细胞比率非常显著卜降(u=3015，
斗
人津医科人学顿上研究’}一学价沦(
尸<0.002)，ERG的b波潜时非常显著延长(r=2.454，p<0.001)及b波振‘1，{，}{l乙
常显著降低(r=4.893，P<0.001)
2.前房内填充0.3~o.6ml PFDL及玻璃体腔内填允0.5~3:nl PFOL术后第
Zmon，角膜内皮细胞密度非常显著下降(t=1 5.192，夕<0.001)，’卜均细J泡一自r干只{{
常显著卜‘降(l一20.582，p<0.001)及六角形细胞比率非常显著卜降向二9619，
尸<0.001)，ERG的b波潜时非常显著延长(t=5.331，尸<0.001)b波抓幅柞常掀著
降低(r=13.862，P<0.001)。
3光镜及电镜检查，术后6h及PFDL少于0.sml术后24h未出现组织细咆
变性坏死等改变，术后7d时，所引起的病理改变为炎症反应及组织细咆变
性，术后第1、Zmon出现角膜上皮水肿，实质细胞坏死，细胞内)侧‘咐广张、
脱颗粒，视网膜感光细胞膜盘变性、萎缩和坏死，细胞间及神经纤维层树突水
肿等严重的不可逆的病理改变，在角膜内皮细胞和视网膜感光细胞发现有髓磷
体的存在。，
4.1边访5~1 lmon，VRS中使用PFDL 245例245只眼术后视网11芡艾位212
例212只眼，有效率86.53%，其巾复杂性RD!75例175只眼术后视网脱女位
一45例一45只眼，有效率84.57%。术
Objective : Perflurocarbon liquids is an important vitreous substitute in Vitreoretinal Surgery(VRS), Perfluorodecalin (PFDL) is one kind of Perflurocarbon ,and is fully fluorinated, synthetic, transparent compounds with high gravity, low viscosity , high boiling point and strong ability of combination with oxygen , can float lens and foreign bodies ,flatten and immobilize retina, reduce injuries in operation , be suitable as an intraoperative tool during VRS , and has been widely used in VRS , as to the toxicity of PFDL to cornea and retina ,at present the studies were clinic ,and there were many unclear problem . Our studies include animal experiment and clinic studies ,a way of ocular injection of PFDL were used in animal experiment ,in order to study the toxicity of PFDL , and study the relationship between the toxicity of PFDL and period of retention, amount of intraocular retention , the mechanism of PFDL toxicity and study the means of avoiding intraocul
ar remnent ,we estimated the histopathologic and ultrastructure change of cornea, angle of anterior chamber, retina and optic nerve of ribbit .
and also by means of Corneal specular microscope , elcctroretinogram(ERG) ,
ultrasound biomicroscopy(UBM ) and visual evoked potcntial(VEP)
In our clinic studies we evaluated the effect of PFDL in VRS treating
complicated retinal detachment(RD), proliferative diabetic retinopathy (PDR),
vitreous hemorrhage, complication of VRS , RD after silicone oil tamponades ,
and observed whether the remnent of PFDL could cause lesion and infection , give
means of preventing ocular remnent of PFDL.
Method : Both animal experimental study and clinic study were used to
study the injury of PFDL to ocular tissue .
1 The animal experimental study of application of PFDL in ocular tissue 32 health ribbits were used ,and were divided into anterior
chamber group and vitreous cavity group by random , different amount of PFDl. were injected into anterior chamber and vitreous cavity, 6h 24h 72h 7d, Imon and 2mons after operation ,(). slit-lamp microscope and indirect ophthalmoscope were used to exam cornea > iris x character of PFDL , hole and detachment of retina.(2). ERG and visual VHP were used to exam the function of retina and optic nerve. (3) Corneal specular microscope were used to exam the function and shape of corneal endothelium .(4).UBM were used to exam the change of cornea > iris and angle of anterior chamber. (5).Cornea > angle of anterior chamber retina and optic nerve were studied by light microscopy and transmission electric microscopy .
2. The clinic study of application of PFDL in ocular tissue 245 clinical cases were studied ,among them were complicated RD 175 eyes PDR 21 eyes, vitreous hemorrhage caused by other reason 27 eyes acute retinal necrosis syndrome(ARN) 2 eyes endophthalmia 3 eyes Coats disease 1 eye , old choroid hemorrhage 1 eye complication of VRS 6 eyess RD after silicone oil tamponades 9 eyes. VRS involving the peeling of pre-retinal membrane PFDL injection endolaser fluid air exchange and inert gas or silicone oil tamponades . Probed the way of avoiding remnent of PFDL in VRS , "permutation of PFDL after air-fluid exchange was used in macular hole or posterior pole hole,that is air-fluid exchange first to flatten retina, then PFDL was injected , "part air-fluid exchange associate with the use of PFDL"was used in grand retina tear, that is part of PFDL was injected first, then air-fluid exchange,and silicone oil or air exchange with PFDL ; " PFDL was used step by step in 360皉etinotomy ", that is part stiff retina was incised , then injected part PFDL ,incise stiff retina step by step ,peel proliferative membrane and draging tissue ,then injected PFDL, to avoid shifting of retina and PFDL flowing into subretina. Slit-lamp microscope and
indirect ophthalmoscope were used to exam the change of cornea, iris and retina , and cases of remnent were also observed.
方法：本研究采用动物实验和临床的方法，探讨PFDL对眼组织的损害作用。
1．全氟萘烷液在眼内应用的实验研究
选择健康家兔32只，随机分为前房及玻璃体腔两组，填充不同剂量的PFDL，在填充术后6h、24h、72h、7d、1mon、2mon分别进行以下实验观察：(1)．采用裂隙灯显微镜、间接检眼镜观察角膜透明度、虹膜有无新生血
天津医科大学硕士研究生学{方沦之
管、PFDL的性状、视网膜有无裂孔及脱离等改变。(2)采用ERG及VEP检改
视网膜及视神经的功能改变。(3)采用角膜内皮显微镜观察角!!莫内皮锁‘:i!:拈
况。(4)采用超声生物显微(ultrasound biomicroscopy，UBM)检查眼前、、的‘，父，Jk.、
(5)采用电镜及光镜检查，对角膜、前房角、视网膜及视神经等组织标本进行
超微结构砂!;究。，
2.全氟蔡烷液在眼内应用的临床研究
总结研究在VRS中应用PFDL治疗临床病例245例245只眼，上鲜，!，义杂
性RD 1 75例1 75只眼、PDRZI例21只眼、其它原因的玻璃体积!{{1.27例27三七
眼、急性视I冈膜坏死(aeute retinal neerosis，从N)2例2只眼、眼内炎3例3三乏
眼、Coats病1例1只眼、陈旧性脉络膜大出血1例1只眼、处理VRS后井发
症6例6只眼、硅油下RDg例9只眼。术中采用玻璃体切割，!摸剥离，PFOL
使用，眼内i放光.气液交换，惰性气体及硅油眼内填充等)’J法，、探讨在VRS
中应用PFDL防止眼内存留的方法，即在复杂性RD的VRS中为防比pFOL残
留和PFDL进入视网膜下，对黄斑裂孔或后极部裂孔患者采用“之一毛液交换后.汽
换PFDL法”，先行气液交换，铺平视网膜，再注入PFDL:对卜.人裂孔性
RD采川“PFDL联合部份气液交换法”，少七注入部份 PFDL，}I少亏J几部分‘七液交
换，作硅油或气体与PFDL交换;对3600视网膜切开患者采川“逐步使川
PFDL法”，先切开部分僵硬的视网膜，注入部份PFDL，逐步切川川心子卿可
膜，剥离增殖膜及牵拉组织，不断注入PFDL，}访l卜视网膜移位和PFDL进入视
网膜下。采用裂隙灯显微镜、间接检眼镜等方法观察术中使用PFDL的病例角
膜、虹膜、视网膜等改变，及随访观察PFDL残留病例。
结果:
1前房内填充0.3~o.6ml及玻璃体腔内填充0.5~3m!PFOL术后第
lmon，角膜内皮细胞密度非常显著下降(r=11471，尸<0.001)，平均乡11胞一!z一积
非常显著下降(t=12.393，p<0.001)及六角形细胞比率非常显著卜降(u=3015，
斗
人津医科人学顿上研究’}一学价沦(
尸<0.002)，ERG的b波潜时非常显著延长(r=2.454，p<0.001)及b波振‘1，{，}{l乙
常显著降低(r=4.893，P<0.001)
2.前房内填充0.3~o.6ml PFDL及玻璃体腔内填允0.5~3:nl PFOL术后第
Zmon，角膜内皮细胞密度非常显著下降(t=1 5.192，夕<0.001)，’卜均细J泡一自r干只{{
常显著卜‘降(l一20.582，p<0.001)及六角形细胞比率非常显著卜降向二9619，
尸<0.001)，ERG的b波潜时非常显著延长(t=5.331，尸<0.001)b波抓幅柞常掀著
降低(r=13.862，P<0.001)。
3光镜及电镜检查，术后6h及PFDL少于0.sml术后24h未出现组织细咆
变性坏死等改变，术后7d时，所引起的病理改变为炎症反应及组织细咆变
性，术后第1、Zmon出现角膜上皮水肿，实质细胞坏死，细胞内)侧‘咐广张、
脱颗粒，视网膜感光细胞膜盘变性、萎缩和坏死，细胞间及神经纤维层树突水
肿等严重的不可逆的病理改变，在角膜内皮细胞和视网膜感光细胞发现有髓磷
体的存在。，
4.1边访5~1 lmon，VRS中使用PFDL 245例245只眼术后视网11芡艾位212
例212只眼，有效率86.53%，其巾复杂性RD!75例175只眼术后视网脱女位
一45例一45只眼，有效率84.57%。术
Objective : Perflurocarbon liquids is an important vitreous substitute in Vitreoretinal Surgery(VRS), Perfluorodecalin (PFDL) is one kind of Perflurocarbon ,and is fully fluorinated, synthetic, transparent compounds with high gravity, low viscosity , high boiling point and strong ability of combination with oxygen , can float lens and foreign bodies ,flatten and immobilize retina, reduce injuries in operation , be suitable as an intraoperative tool during VRS , and has been widely used in VRS , as to the toxicity of PFDL to cornea and retina ,at present the studies were clinic ,and there were many unclear problem . Our studies include animal experiment and clinic studies ,a way of ocular injection of PFDL were used in animal experiment ,in order to study the toxicity of PFDL , and study the relationship between the toxicity of PFDL and period of retention, amount of intraocular retention , the mechanism of PFDL toxicity and study the means of avoiding intraocul
ar remnent ,we estimated the histopathologic and ultrastructure change of cornea, angle of anterior chamber, retina and optic nerve of ribbit .
and also by means of Corneal specular microscope , elcctroretinogram(ERG) ,
ultrasound biomicroscopy(UBM ) and visual evoked potcntial(VEP)
In our clinic studies we evaluated the effect of PFDL in VRS treating
complicated retinal detachment(RD), proliferative diabetic retinopathy (PDR),
vitreous hemorrhage, complication of VRS , RD after silicone oil tamponades ,
and observed whether the remnent of PFDL could cause lesion and infection , give
means of preventing ocular remnent of PFDL.
Method : Both animal experimental study and clinic study were used to
study the injury of PFDL to ocular tissue .
1 The animal experimental study of application of PFDL in ocular tissue 32 health ribbits were used ,and were divided into anterior
chamber group and vitreous cavity group by random , different amount of PFDl. were injected into anterior chamber and vitreous cavity, 6h 24h 72h 7d, Imon and 2mons after operation ,(). slit-lamp microscope and indirect ophthalmoscope were used to exam cornea > iris x character of PFDL , hole and detachment of retina.(2). ERG and visual VHP were used to exam the function of retina and optic nerve. (3) Corneal specular microscope were used to exam the function and shape of corneal endothelium .(4).UBM were used to exam the change of cornea > iris and angle of anterior chamber. (5).Cornea > angle of anterior chamber retina and optic nerve were studied by light microscopy and transmission electric microscopy .
2. The clinic study of application of PFDL in ocular tissue 245 clinical cases were studied ,among them were complicated RD 175 eyes PDR 21 eyes, vitreous hemorrhage caused by other reason 27 eyes acute retinal necrosis syndrome(ARN) 2 eyes endophthalmia 3 eyes Coats disease 1 eye , old choroid hemorrhage 1 eye complication of VRS 6 eyess RD after silicone oil tamponades 9 eyes. VRS involving the peeling of pre-retinal membrane PFDL injection endolaser fluid air exchange and inert gas or silicone oil tamponades . Probed the way of avoiding remnent of PFDL in VRS , "permutation of PFDL after air-fluid exchange was used in macular hole or posterior pole hole,that is air-fluid exchange first to flatten retina, then PFDL was injected , "part air-fluid exchange associate with the use of PFDL"was used in grand retina tear, that is part of PFDL was injected first, then air-fluid exchange,and silicone oil or air exchange with PFDL ; " PFDL was used step by step in 360皉etinotomy ", that is part stiff retina was incised , then injected part PFDL ,incise stiff retina step by step ,peel proliferative membrane and draging tissue ,then injected PFDL, to avoid shifting of retina and PFDL flowing into subretina. Slit-lamp microscope and
indirect ophthalmoscope were used to exam the change of cornea, iris and retina , and cases of remnent were also observed.
引文
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