曲安奈德对兔视网膜组织和细胞形态学影响的实验研究

目的 观察玻璃体内注射去除溶媒后的两种商用曲安奈德（TA）对兔眼视网膜结构的影响及其与剂量的关系。设计 实验研究。研究对象 新西兰白兔21只。方法 将实验动物分为A（药物A）、B（药物B）、C（平衡盐溶液）三组,A组分为A1、A2、A3三个亚组,B组分为 B1、B2两个亚组,C组分为C1、C2两个亚组。用梯度离心法去除两种商用TA注射液（药物A、药物B）中的溶媒,获取TA颗粒。向A1、A2和A3组兔右眼玻璃体内分别注入4 mg、20 mg和40 mg药物A;向B1、B2组兔右眼玻璃体内分别注入4 mg和20 mg的药物B;向C1和C2组兔右眼玻璃体内分别注入0.1 ml和0.2 ml平衡盐溶液作为对照。注药前、后行眼前段及眼底检查。术后8周眼球摘除在光镜下行视网膜组织学检查及用透射电镜观察视网膜细胞结构。主要指标 眼底形态、视网膜光镜结构、光感受器细胞电镜结构。结果 注射后8周所有注射眼均未出现眼前段及眼底异常。光镜检查显示：与未注射眼相比,C组及A组兔眼视网膜结构大致正常,B组兔眼光镜下出现内层、外层视网膜结构紊乱,B2组较B1组更为明显;透射电镜检查显示：与未注射眼比较,C1、C2组兔眼部分线粒体出现水肿、嵴断裂,C1组较C2组更为明显,膜盘形态及光感受器细胞核形态大致正常;A1、A2、A3组兔眼可见轻度光感受器膜盘水肿,而细胞核、线粒体结构无明显改变,且线粒体嵴随注射剂量增加排列更为整齐;B1、B2与未注射眼、C组以及A组相比,光感受器膜盘明显水肿,细胞核皱缩和广泛线粒体水肿、嵴断裂缺失,B2组较B1组改变更为明显。结论 本研究中两种TA对视网膜的影响不同。两种TA注射眼中可见随剂量加重的视网膜损害,不排除某些损害由难以彻底去除的溶媒成分引起。玻璃体内注射TA时应充分权衡其治疗效应与毒性效应。TA提取颗粒可能对视网膜光感受器细胞线粒体代谢功能具有潜在的保护或加强作用。     

曲安奈德联合激光光凝治疗视网膜静脉阻塞继发黄斑水肿

目的：观察玻璃体腔内曲安奈德( trialcinolone acetonide, TA)注射联合黄斑格栅样光凝治疗视网膜静脉阻塞引起黄斑水肿的疗效分析。
　　方法：检眼镜、眼底血管造影( FFA )、光学相干断层扫描( OCT)检查证实的由视网膜静脉阻塞引起的黄斑水肿患者35例35眼,玻璃体内注射TA 2lg,1~4wk内黄斑水肿减轻后行黄斑格栅样光凝,随访6lo,观察视力、眼压、晶状体,OCT 观察黄斑厚度改变,FFA 观察眼底毛细血管渗漏情况。
　　结果：视网膜中央静脉阻塞( central retinal vein occlusion, CRVO)中非缺血型10眼,缺血型14眼;视网膜分支静脉阻塞( branch retinal vein occlusion, BRVO)中非缺血型4眼,缺血型7眼。最终视力提高者19眼,不变者11眼,比术前降低者5眼。 OCT检查黄斑中心凹形态恢复正常者9眼,FFA提示黄斑区荧光素渗漏与术前相比消失或明显减轻;黄斑囊样水肿明显改善者21眼,FFA 提示渗漏比术前减轻;无改善者5眼,FFA 提示黄斑区渗漏比术前加重或不变。
　　结论：玻璃体腔内注射TA 2 lg联合黄斑格栅样光凝治疗视网膜静脉阻塞继发黄斑水肿,可以明显减轻由静脉阻塞引起的黄斑水肿,并提高患者视力,是一种有效可行的方法。     

玻璃体内注射曲安奈德治疗Coats病渗出性视网膜脱离

目的观察玻璃体内注射曲安奈德（TA）治疗Coats病渗出性视网膜脱离的疗效。方法12例（12只眼）经眼底检查、荧光素眼底血管造影（FFA）和B超确定的Coats病引起的视网膜脱离患者接受玻璃体内注射40mS／1ml的TA0．1ml治疗，平均随访10．2个月，对比观察治疗前后患眼视力、眼压、视网膜复位情况。结果12只眼中10只眼视网膜复位，占83．3％，随访3个月2只眼因视网膜未完全复位，再次行玻璃体内注射TA；术后视力均有不同程度提高；2只眼眼压升高发生于用药后1周至2个月，经局部用B受体阻滞剂眼压控制正常；1只眼白内障发展。结论玻璃体内注射TA是治疗Coats病引起的渗出性视网膜脱离的有效手段。     

光学相干断层扫描血管成像(OCTA)和荧光素血管造影(FFA)对比观察增生型糖尿病视网膜病变(PDR)

目的 运用光学相干断层扫描血管成像(optical coherence tomography angiography,OCTA)和荧光素血管造影(fundusfluorescein angiography,FFA)对比观察增生型糖尿病视网膜病变(proliferating diabetic retinopathy,PDR)的临床特征,分析OCTA与FFA对PDR患眼眼底病变检出的一致性.方法 回顾性病例研究.选择PDR患者25例(36眼),每例患者均行OCTA和FFA检查,并且两项检查间隔时间不超过2h.对比观察记录PDR患眼在OCTA和FFA图像中黄斑拱环结构改变、黄斑水肿、视网膜微血管瘤、视网膜新生血管、视网膜无灌注区5种眼底病变的影像学特征,并分析两种检查方法对上述眼底改变检出的一致性.结果 PDR患眼的OCTA特征主要为黄斑拱环结构改变区视网膜浅层毛细血管扩张迂曲、深层中心凹无血管区扩大,黄斑水肿区视网膜浅层血管迂曲扩张、视网膜深层片囊状弱信号,视网膜微血管瘤区浅层、深层毛细血管局部囊样扩张膨大或梭形改变,视网膜新生血管区浅层、深层不规则异常血管网状结构,视网膜无灌注区片状弱信号;PDR患眼的FFA图像特征主要为黄斑拱环结构改变区周围血管扩张弯曲,黄斑水肿区、视网膜微血管瘤区和视网膜新生血管区造影期强荧光,视网膜无灌注区表现和OCTA相似.OCTA检查发现PDR患眼黄斑拱环结构改变、黄斑水肿、视网膜微血管瘤、视网膜新生血管、视网膜无灌注区分别为26眼、26眼、25眼、13眼、30眼;FFA检查发现5种眼底病变依次为20眼、28眼、28眼、12眼、30眼;OCTA与FFA检查对PDR患眼黄斑拱环结构改变、黄斑水肿、视网膜微血管瘤检出的一致性一般(Kappa=0.416、0.705、0.646,均为P＜0.01),对视网膜新生血管、视网膜无灌注区检出的一致性较好(Kappa=0.816、0.800,均为P＜0.01).结论 OCTA与FFA能较好地观察到PDR患眼5种眼底病变,并对PDR患眼的部分眼底病变的检出具有良好的一致性.     

玻璃体腔注射Avastin治疗视网膜中央静脉阻塞黄斑水肿的临床观察

目的:观察不同剂量、不同次数玻璃体腔注射avastin(beyacizumab)治疗视网膜中央静脉阻塞(central retinal veinocclusion,CRVO)伴黄斑水肿(macularedema,ME)的临床效果。方法:回顾分析2007-4/2009-10我院就诊,经眼底检查、荧光眼底血管造影(FFA)、光学相干断层扫捕(OCT)检查确诊的CRVO伴ME患者72例75眼,A组38例39眼,其中A1组20例21眼玻璃体腔内注射avastin 1.25mg(0.05mL);A2组18例18眼玻璃体腔内注射avastin1.25mg后间隔4wk再次重复治疗。B组34例36眼,其中B1组16例16眼玻璃体腔内注射avastin 2.0mg(0.08mL);B2组18例20眼玻璃体腔内注射avastin2.0mg后间隔4wk再次重复治疗。对比每次治疗前、及治疗后1,2,4wk的视力、眼压、眼底,治疗前和治疗后4wk的FFA表现和OCT测量黄斑中心视网膜厚度。结果:72例75眼中有58例61眼视力和黄斑水肿改善,A2组与A1组、B2组与B1组比较差异有统计学意义(P<0.01),A1组与B1组、A2组与B2组比较差异没有统计学意义。结论:玻璃体腔内注射avastin可改善视网膜中央静脉阻塞继发黄斑水肿患者的视力和黄斑水肿高度,重复治疗效果更明显,但增加剂量并不会明显改善黄斑水肿高度。     

玻璃体内注射庆大霉素致视网膜损伤的实验研究Ⅰ．组织病理学观察

为探讨庆大霉素对视网膜的毒性作用和评估玻璃体内注射庆大霉素的安全剂量，采用眼底镜观察及光镜、电镜技术对注射５种不同剂量庆大霉素的青紫蓝兔视网膜标本进行观察。结果：３０００μｇ庆大霉素注射后眼底表现为视盘水肿，后极部视网膜大片坏死，镜下视网膜组织形态严重破坏；５０～５００μｇ剂量注射引起后极部视网膜色素改变，组织损伤早期局限在视网膜内层，晚期全层受累。提示庆大霉素对视网膜的损伤程度随注入剂量增加而加重，即使５０μｇ的微小剂量仍可产生视网膜损伤。     

眼挫伤荧光素眼底血管造影临床分析

目的 分析眼挫伤眼底改变及荧光素眼底血管造影(FFA)的表现.方法 对268例(339只眼)眼挫伤经直接检眼镜和三面镜检查及FFA检查.结果 眼挫伤视功能严重受损的主要原因是视网膜、视神经受损,常见的有视网膜震荡、视网膜出血、黄斑裂孔、脉络膜破裂、出血,视网膜脱离和视神经损伤.其中以视网膜震荡多见.结论 对于眼挫伤患者,只要屈光间质清晰,都应检查眼底,行FFA检查,以判断眼底病损伤部位及损害程度.     

家族性渗出性玻璃体视网膜病变的荧光素眼底血管造影分析

目的分析家族性渗出性玻璃体视网膜病变的眼底表现及荧光素眼底血管造影(FFA)特征。方法收集我院诊治的家族性渗出性玻璃体视网膜病变患者,进行眼底照相及FFA检查,进行对比分析。结果眼底特征性表现为,视盘颞侧一条索样皱襞,该部分视网膜血管分支密集、数目较多,终止与周边视网膜。周边视网膜检查可见一边界清晰的片状灰白色病灶,此处视网膜血管迂曲扩张。FFA特征为:周边视网膜FFA显示血管分支增多、迂曲扩张,呈"树枝样"改变,走行平直。血管末端发生吻合、呈扇形终止,此部分血管渗漏。结论眼底检查、FFA结合患者病史、家族史可明确诊断家族性渗出性玻璃体视网膜病变。     

全氟全氢菲在猕猴玻璃体腔内充填的实验研究

目的:评估 全氟全氢 菲(perfluoroperhydrophenan-threne,即 vitreon)在猕猴玻璃体腔内充填对视网膜的毒性作用和眼前段的影响。方法:对 4 只猕猴 8 眼进行三通道玻璃体切除术,术毕于 1 眼玻璃体腔内注入平衡盐液作为对照,在7 眼内注入 vitreon1mL 分别达术后 2,4wk (各 2眼),,,9wk(各 1 眼)。观察术后眼前段和玻璃体 5 6腔内炎症反应,测量术前、术后眼压,并做荧光素眼底血管造影检查,最后对视网膜组织行光镜和透射电镜检查。结果:所有眼在术后1wk内均表现为轻度的炎症反应,vitreon在玻璃体腔内形成分散的小泡。整个实验过程角膜和晶状体均透明。术后眼压与术前相比无显著变化。各时期荧光素眼底血管造影显示无血管渗漏,光镜检查视网膜大体结构和房角结构正常,透射电镜显示vitreon在玻璃体腔内存留2wk时上、下方视网膜内节即出现线粒体肿胀,下方视网膜双极细胞和神经节细胞轻度肿胀,且随充填时间延长损害加重。经统计学分析,上、下方视网膜损害差别无显著性意义(P >0.05)。结论:全氟全氢菲在猕猴玻璃体腔内存留9wk对眼前节和视网膜微循环没有影响。充填2wk可致视网膜超微结构的改变,损害主要累及视网膜内节和双极细胞、神经节细胞,故不适于术后较长时间的充填。     

玻璃体内注射庆大霉素致视网膜损伤的实验研究I．组织病理学观察

为探讨庆大霉素对视网膜的毒性作用和评估玻璃体内注射庆大霉素的安全剂量,采用眼底镜观察及光镜、电镜技术对注射5种不同剂量庆大霉素的青紫蓝兔视网膜标本进行观察。结果： 3 ooo/μg庆大霉素注射后眼底表现为视盘水肿,后极部视网膜大片坏死,镜下视网膜组织形态严重破坏;50～500μg剂量注射引起后极部视网膜色素改变,组织损伤早期局限在视网膜内层,晚期全层受累。提示庆大霉素对视网膜的损伤程度随注入剂量增加而加重,即使50μg的微小剂量仍可产生视网膜损伤。 （中华眼底病杂志,1994,10：167-169）     

A moephologic study of retinal toxicity induced by triamcinolone acetonide vehicles in rabbit eyes

PURPOSE: To evaluate the toxic effects of two triamcinolone acetonide (TA) vehicles on rabbit retina at different volumes. METHODS: Vehicle A and B were prepared from two TA injections by centrifugation. Thirty-six New Zealand white rabbits were intravitreally injected with vehicle A, B, or balanced saline solution at 0.1 mL or 0.2 mL respectively. The eyes were examined by indirect ophthalmoscope, light microscope, and transmission electron microscope up to week 8 postinjection. RESULTS: Eyes with vehicle A appeared normal under the ophthalmoscope, but showed disorganization in retinal inner nuclear layer and photoreceptor layer in pathologic analyses. Eyes with vehicle B displayed more significant retinal changes including retinal hemorrhage, vascular narrowing, myelinated fiber edema, retinal necrosis and atrophy, and photoreceptor apoptosis. There was an increase in degree of the above damages as the volume of either vehicle increased. CONCLUSION: Both vehicle A and B caused volume-related toxicity in rabbit retina. The intensity of the toxic effects of different vehicles may differ. Reducing or decanting the vehicles should be considered before intravitreal use of TA injections.     

TA联合激光治疗视网膜静脉阻塞黄斑水肿的临床观察

目的:观察玻璃体腔内注射曲安奈德联合激光光凝治疗视网膜静脉阻塞引起的黄斑水肿的有效性和安全性。方法:患者38例38眼经眼底镜检查、眼底荧光素血管造影(fundus fluorescein angiography,FFA)及光学相干断层扫描(optical coherence tomography,OCT)检查明确诊断的视网膜静脉阻塞引起的黄斑水肿,玻璃体腔内注入曲安奈德4mg(0.1mL),术后1～2mo时行视网膜激光光凝,随访3～9mo,观察视力、眼压、眼底情况及视网膜厚度变化。结果:视力提高36眼,视力无变化2眼。视力<0.1者3眼,0.1～0.3者11眼,0.3～0.5者17眼,>0.5者7眼。4例患者眼压不同程度升高,予以局部降眼压药物治疗后,术后2～5mo眼压恢复正常,未发生1例视网膜毒性反应。结论:曲安奈德联合激光可以安全、有效治疗视网膜静脉阻塞引起的黄斑水肿,提高患者视功能。     

头孢哌酮/舒巴坦兔玻璃体腔注射视网膜毒性的研究

目的 确定头孢哌酮／舒巴坦在兔玻璃体腔注射的安全有效剂量，以指导人玻璃体腔用药。方法 成年健康青紫兰兔15只，随机分为5组，每组3只(6眼)。每组注射头孢哌酮／舒巴坦质量浓度分别为：0、5、10、20、40mg／0．1mL。注药后1、2、4、8、12、24h各观察1次，以后每天观察1次。比较注药前及注药后第1、3、7、14d ERG检查结果。2周后行大体标本观察及光镜和透射电镜观察。对ERG的a、b波振幅变化用方差分析进行检验。结果 5和10mg药物注射组FERG各波振幅和视网膜组织学检查均无明显改变，但在20、40mg剂量组，头孢哌酮／舒巴坦在兔玻璃体腔注射后可见FERG各波的明显下降和电镜下视网膜各层细胞的水肿和空泡样变。结论 10mg／0．1mL的头孢哌酮／舒巴坦玻璃体腔注射是一个安全剂量。     

玻璃体腔注射台盼蓝对兔视网膜组织学的影响

目的探讨不同质量浓度的台盼蓝作用一定时间后视网膜的组织病理学改变。方法12只新西兰白兔随机分为3组,每组4只。对经气体压迫玻璃体切割术的兔右眼玻璃体腔注入0.1ml质量浓度分别为0.06%、0.1%和0.2%的台盼蓝溶液。左眼玻璃体腔注入0.1ml平衡盐溶液作为对照。术前和术后间接检眼镜检查、监测眼压。术后4周取视网膜标本,行光镜及透射电镜检查。结果光镜下3个组兔视网膜各层组织结构无明显改变。电镜下,0.06%组下方视网膜超微结构未见明显异常;0.1%组改变较轻,大部为可逆性改变;0.2%组改变明显,大部损伤是不可逆性的。结论较高质量浓度的台盼蓝与视网膜长时间接触可致视网膜超微结构的改变。     

Safety of intravitreal triamcinolone acetonide:an electrophysiologic and histopathological study in rabbits

AIM: To evaluate the retinal safety of various doses of intravitreal triamcinolone acetonide (TA) in rabbits.Methods: Thirty New Zealand albino rabbits were divided into five groups (six animals each). In group 1 (control group), each animal received a single intravitreal injection of 0.1mL phosphate buffered saline. In groups 2, 3, 4 and 5, each rabbit received a single intravitreal injection of 4, 8, 16 and 32mg of TA, respectively. Each dose was contained in 0.1mL phosphate buffered saline. Clinical ocular examinations were performed before the injection and on the 1st, 3rd, 10th and 17th post-injection days. A standard dark adapted electroretinogram (ERG) was obtained before injection and on the 3rd, 10th and 17th post-injection days. After 17d, animals were sacrificed and their eyes prepared for pathological examination.RESULTS:By monitoring ERG as a functional index for the retina, intravitreal injection of 4mg TA showed no significant ERG changes. At doses of 8, 16 and 32, hyper-abnormal responses in a- and b- waves of ERG were detected on the 3rd post-injection day. These changes gradually returned back to normal limits after 17d. Histopathological examination of the retina of all animals showed no pathological changes.CONCLUSION: High doses of intravitreal TA seemed to have enhancing effects on the retinal function with gradual return to normal limits with no pathological changes detected in examined eyes.     

不同疗法治疗视网膜静脉阻塞所致黄斑水肿的疗效评价

目的:比较普通治疗和玻璃体腔注射曲安奈德(TA)治疗视网膜静脉阻塞所致黄斑水肿的疗效。方法:经眼科常规检查,眼底荧光造影(FFA)和光学相干断层扫描(OCT)确诊的视网膜静脉阻塞所致黄斑水肿共75例,患者被分成普通治疗组(血塞通、葛根素静点2wk+山莨蓉碱、地塞米松球后注射1wk+出院后口服活血化瘀类药物12wk)和玻璃体腔注射TA组(血栓通、葛通素静点2wk+抗生素滴眼液滴眼3d+玻璃腔注射TA+出院后口服活血化瘀药物12wk)。普通治疗组31例,玻璃体腔注射TA组44例,两组在术前年龄,病程,眼压,最佳矫正视力(BCVA),中心视网膜厚度(CMT)方面无统计学差异,比较治疗后4,12wk眼压,BCVA,CMT,的改变。结果:普通治疗组和玻璃体腔注射TA组在治疗后12wk均改善中心视网膜厚度,玻璃体腔注射TA组较普通治疗组效果显著。4,12wk均能改善视力,组间无显著差别。玻璃体腔注射TA组术后4wk眼压升高(>5mmHg),组间显著差异,12wk眼压回落,组间无显著差异。结论:普通治疗组和玻璃体腔注射TA组均能明显减轻视网膜静脉阻塞所致黄斑水肿,改善视力,但是术后眼压升高值得注意。     

地塞米松对玻璃体积血兔视网膜病理变化的影响

目的:观察地塞米松(dexamethasone,Dxm)对兔玻璃体积血后视网膜病理变化的影响。方法:白兔24只,随机分为实验对照组(A),积血组(B)和Dxm干预组(C),每组8只。A组玻璃体内注入生理盐水0.2mL,B组、C组玻璃体内注入自体血0.2mL;注入后1,24,48h,A和B组给予生理盐水3mL/kg,C组给予Dxm3mg/kg。分别于造模后3,7,14,21d随机处死每组中的2兔4眼观察视网膜病理变化。结果:A组所有时间点,B组3,7d,C组3,7,14d视网膜形态正常。B组14d神经节细胞、内丛状层水样变性;21d视网膜内界膜不完整,内、外核层细胞和光感受器内、外节水样变性。C组21d神经节细胞染色变淡,内丛状层、内核层水样变性。结论:玻璃体积血可引起视网膜细胞水样变性,Dxm可缓解玻璃体积血后视网膜水样变性。     

Safety of intravitreal triamcinolone acetonide:an electrophysiologic and histopathological study in rabbits

AIM

To evaluate the retinal safety of various doses of intravitreal triamcinolone acetonide (TA) in rabbits.

Methods

Thirty New Zealand albino rabbits were divided into five groups (six animals each). In group 1 (control group), each animal received a single intravitreal injection of 0.1mL phosphate buffered saline. In groups 2, 3, 4 and 5, each rabbit received a single intravitreal injection of 4, 8, 16 and 32mg of TA, respectively. Each dose was contained in 0.1mL phosphate buffered saline. Clinical ocular examinations were performed before the injection and on the 1st, 3rd, 10th and 17th post-injection days. A standard dark adapted electroretinogram (ERG) was obtained before injection and on the 3rd, 10th and 17th post-injection days. After 17d, animals were sacrificed and their eyes prepared for pathological examination.

RESULTS

By monitoring ERG as a functional index for the retina, intravitreal injection of 4mg TA showed no significant ERG changes. At doses of 8, 16 and 32, hyper-abnormal responses in a- and b- waves of ERG were detected on the 3rd post-injection day. These changes gradually returned back to normal limits after 17d. Histopathological examination of the retina of all animals showed no pathological changes.

CONCLUSION

High doses of intravitreal TA seemed to have enhancing effects on the retinal function with gradual return to normal limits with no pathological changes detected in examined eyes.     

Retinal toxicity of intravitreal triamcinolone acetonide at high doses in the rabbit

In order to study acute retinal toxicity of intravitreal triamcinolone acetonide (TA) at high doses in an animal model, thirty New Zealand albino rabbits were injected with intravitreal TA. The animals were divided in five groups: Group 1 received an intravitreal injection of 0.1 mL balanced salt solution; Group 2, 0.1 mL of the solvent (0.99 mg of benzyl alcohol); Group 3, received 4 mg/0.1 mL TA; Group 4, 20mg/0.1 mL TA; and Group 5, 30 mg/0.1 mL TA. A standard light and dark adapted electroretinogram (ERG) was obtained prior and 28 days after the injection. The animals were sacrificed 28 days after the injection and the eyes were enucleated and examined by electron (EM) and light microscopy (LM) using hematoxylin-eosin, Nissl fluorescent, and immunohistochemistry (glial fibrillary acidic protein). No statistically significant differences in ERG before and 28 days after the injection were found. LM and EM did not show retinal damage in any animal. One eye developed bacterial endophthalmitis 14 days after the injection. Intravitreal TA up to 30 mg does not seem to have acute toxic effects on the function (ERG) or the structure (LM, EM) of the retina of albino rabbits.