维甲酸硅油防治实验性增殖性玻璃体视网膜病变

目的：评价维甲酸硅油对免眼实验性增殖性玻璃体视网膜病变的预防作用。 方法：新西兰白兔30只(58只眼)，随机分为三组：对照组(20只眼注入硅油或平衡盐溶液)、维甲酸硅油5μg/ml组(18只眼)、维甲酸硅油10μg/ml组(20只眼)。行气体压迫玻璃手术3天后，所有实验眼玻璃体腔内注入2X10⁵个成纤维细胞，再分别注入硅油或平衡盐溶液0.5ml。以检眼镜观察牵引性视网膜脱离发生情况，共4周。 结果：28天时，对照组、维甲酸硅油5μg/ml组、维甲酸硅油10μg/ml组的牵引性视网膜脱离发生率分别为80.00%、44.44%、30.00%，两组维甲酸硅油组与对照组相比经统计学处理差异均有显著性(χ²检验，P<0.05)。 结论：浓度为5μg/ml及10μg/ml的维甲酸硅油能够有效地预防增殖性玻璃体视网膜病变的发生。 （中华眼底病杂志，1997，13：174-176）     

维甲酸纳米粒的视网膜毒性实验研究

目的了解维甲酸纳米粒对兔视网膜是否产生毒性.方法30只青紫蓝兔的60眼随机分为5组,每组12眼,正常组不注药,其余分别向玻璃体腔注入维甲酸纳米粒5、10、20mg·L-1以及BSS(对照组)0.3mL,以检眼镜、电生理、光镜和电镜检查观察视网膜变化情况.结果注药后7d,光镜检查20mg·L-1组出现神经节细胞的空泡样变,电镜及电生理检查未见异常,14d时恢复正常;至28d,未发现各浓度的维甲酸纳米粒对视网膜产生毒性作用.结论玻璃体腔注入浓度≤20mg·L-1的维甲酸纳米粒,对视网膜不会产生毒性作用.     

维甲酸纳米粒对视网膜毒性作用的实验分析

目的分析维甲酸纳米粒对兔视网膜毒性作用的影响因素。方法30只青紫蓝兔随机分为5组，包括正常组、10μg／mL、20μg／mL维甲酸纳米粒组、15μg／mL、10μg／mL丙酮组。分别于玻璃体腔注药后7、14、28d用检眼镜观察眼底变化，并行双眼视网膜电图(ERG)检查，摘除眼球行组织学观察。结果7d时，20μg／mL维甲酸组及15μg/mL丙酮组出现视网膜神经节细胞(RGCs)的空泡样变，但在14d时恢复正常。其余各组视网膜无明显组织学变化。在各组实验中未发现ERG的明显变化。结论20μg／mL维甲酸纳米粒玻璃体腔注射对视网膜是安全的，制剂中质量浓度≤10μg／mL的丙酮残留不会埘兔视网膜产生毒性作用。     

兔眼玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的视网膜毒性研究

目的 观察不同剂量抗血管内皮生长因子单克隆抗体Bevacizumab兔眼玻璃体腔注射的视网膜毒性作用。 方法 16只新西兰无色素兔的32只眼随机分为药物注射组和对照组，药物注射组又根据玻璃体腔注射药物剂量不同分为A、B、C组，玻璃体腔注射Bevacizumab剂量分别为0.05、0.10、0.25 ml，分别含Bevacizumab 1.25、2.50、6.25 mg。对照组玻璃体腔注射0.9％生理盐水0.10 ml。注药后1、2、4周行视网膜电图（ERG）检查。另外 ，在兔眼玻璃体腔注射Bevacizumab后1、2、4周，每组各摘除2只兔眼，行视网膜组织形态及超 微结构的光学显微镜和透射电子显微镜观察。 结果 兔眼玻璃体腔注射 Bevacizumab后1、2、4周，兔眼ERG各项反应波形均正常，振幅均未出现异常改变（P＞0.05）。光学显微镜下观察 ，药物注射组和对照组视网膜各层组织形态在各时间点均未见异常。透射电子显微镜观察， A、B组与对照组无明显差异；C组视网膜光感受器细胞出现部分线粒体损伤，发生肿胀和积 水变，4周时病变无缓解。 结论 单次兔眼玻璃体腔注射Bevacizumab 1.25 mg或2.50 mg是安全的。 （中华眼底病杂志，2008，24：193-196）     

国产硅油对视网膜毒性作用的试验研究

目的观察国产硅油对兔视网膜组织结构和功能的影响。方法健康纯种新西兰白兔28只,12只兔眼玻璃体切除术后玻璃体腔注入国产硅油,为实验组;12只兔眼玻璃体切除术后玻璃体腔注入德国产硅油,为对比组;对照组4只兔眼只将灌注液BSS保留于玻璃体腔。手术后定期裂隙灯、间接检眼镜检查,3月后行视网膜电图检查,3、6月处死动物行组织学和透射电镜检查。结果硅油在玻璃体腔内透明,6月内未见明显乳化现象,可造成晶体后囊的轻微混浊。组织学检查：对照组视网膜各层结构排列整齐,细胞结构正常。实验组、对比组手术后3-6月视网膜各层结构排列整齐,上方视网膜有的可见外丛状层轻微变薄。透射电镜检查：实验组、对比组手术后3～6月视网膜各层结构排列整齐,神经节细胞及内、外核层细胞排列整体,细胞结构正常,6月有的可见外核层细胞外节盘膜的排列轻微紊乱。视网膜电图检查,实验组、对比组硅油术后a、b波波峰有所降低。结论国产硅油（5000cps）性能稳定,玻璃体内填充3～6个月,对视网膜结构和功能影响轻微,与进口硅油对视网膜的影响作用相似,可作眼内长期填充,可进行临床实验。     

t-PA对实验性玻璃体渗出的治疗作用

18只兔眼玻璃体腔内注射自体血浆0.2ml制成的玻璃体渗出模型，随机接受玻璃体内注射组织型纤溶酶原激恬酶(t-PA)或生理盐水，其中10眼玻璃体内注入t-PA 12.5μg，结果6眼的纤维蛋白在6h内清除，另4眼在1d内彻底清除．注入生理盐水的7眼需7d才完全清除。两用从时间上比较，差别有显著性(P<0.05)．经裂隙灯、ERG、光镜及电镜检查未见毒性作用．另1只注入10μg t-PA的兔眼虽然6h内见纤维蛋白凝块溶解，但眼底镜和光镜下已显示视网膜的毒性变化。 （中华眼底病杂志，1994，10：14-16）     

玻璃体腔注射乳酸环丙沙星对视网膜 影响的研究

目的探讨玻璃体腔注射乳酸环丙沙星治疗方法对视网膜组织的安全性。方法24只兔随机分为4组，每组6只。玻璃体腔内分别注入0.1 ml不同浓度的乳酸环丙沙星，浓度分别为：2 500 、5 000、10 000 μg/ml；对照组注射生理盐水0.1 ml。手术后观察眼底表现，分别行光学显微镜、透射电子显微镜等组织学检查和视网膜电图（ERG）视网膜功能检查。结果250、500 μg组光学显微镜检查结果未见异常，超微结构大致正常；1 000 μg 组光学显微镜下可见视网膜内外核层排列不规则，神经节细胞水肿变性或脱失，透射电子显微镜下可见超微结构改变。视网膜功能检查显示，各组ERG的a～b波波幅注药前后无明显差别。结论玻璃体腔注射国产乳酸环丙沙星安全、抗菌谱广，500 μg以下是较为安全的眼内应用剂量。(中华眼底病杂志,2005,21:180-182)     

三种药物在兔外伤性增生性玻璃体视网膜病变中的作用

目的：探讨曲安奈德(TA)、青蒿琥酯(ART)、木犀草素(LU)对外伤性增生性玻璃体视网膜病变(TPVR)的防治作用。

方法：选取青紫蓝兔48只经制作眼球穿通伤及玻璃体腔内注射0.3mL富含血小板血浆的方法制备TPVR动物模型,随机分为4组(n=12),其中对照组玻璃体腔注入0.1mL生理盐水; TA组玻璃体腔注入0.1mL(1mg/mL)曲安奈德; ART组玻璃体腔注入0.1mL(20μg/mL)青蒿琥酯; LU组玻璃体腔注入0.1mL(10μg/mL)木犀草素。术后1、2、3、4wk通过眼底照相和眼部B超观察玻璃体及视网膜增生情况,术后28d采用Western Blot法检测各组兔眼玻璃体液中α-SMA和VIM蛋白表达水平,并经视网膜HE染色观察各组视网膜组织结构情况。

结果：术后28d,TA组、ART组和LU组兔眼TPVR分级均显著低于对照组(P<0.05),且TA组兔眼TPVR分级均显著低于ART组和LU组(P<0.05)。术后28d,TA组、ART组和LU组兔眼玻璃体液中α-SMA和VIM蛋白的表达水平均显著低于对照组(P<0.01)。HE染色结果显示,对照组兔眼视网膜各层排列紊乱,严重扭曲或局部断裂,各层结构不清晰,前膜明显增厚,视网膜明显脱离; LU组兔眼视网膜各层排列轻微扭曲,视网膜前可见炎性渗出,视网膜浅层脱离; ART组兔眼视网膜结构清晰,轻度水肿,可见浅层脱离; TA组兔眼视网膜各层结构清晰,排列尚整齐,局部可见视网膜褶皱,无视网膜脱离。

结论：玻璃体腔内注射曲安奈德、青蒿琥酯及木犀草素均对TPVR具有防治作用,其中曲安奈德效果最明显。     

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。     

t—PA眼内注射对实验性玻璃体出血的治疗观察

对小剂量组织型纤溶酶原激活制(t-PA)重复眼内注射治疗实验性玻璃体出血的疗效进行了观察.14只兔(28只眼)通过向玻璃体内注入0.05ml含枸橼酸钠的自体全血建立玻璃体出血模型。1周后将其随机分为3组，第1组和第2组隔周1次注射5μg或25μg-PA共注射2次(总量10μg或50μg)，第3组按同法接受生理盐水治疗．出血的清除在t-PA治疗组均显著地快于对照组(P<0.05或P<0.01)，但t-PA治疗组间差异无显著性．经ERG，光镜和电镜检查未见视网膜毒性变化。 （中华眼底病杂志，1995，11：185-187）     

Extraction of retinol and cholesterol by intraocular silicone oils

According to their solubility parameters, retinol and its derivatives, as well as cholesterol and other lipophilic substances, are predicted to dissolve in intraocular silicone and fluorosilicone oils. Calf retinas were extracted in vitro with these oils and the oils then analyzed spectrophotometrically. The following levels were found after extraction for 4 and 48 hours, respectively: for retinol, silicone oil, 0.5 and 3.7 micrograms/ml, and fluorosilicone oil, 0.5 and 3.3 micrograms/ml; for cholesterol, silicone oil, 0.5 and 6.4 micrograms/ml, and fluorosilicone oil, 0.8 and 3.7 micrograms/ml. In in vivo experiments, intraocular oils were removed from rabbit eyes at 4 days to 10 weeks after injection. The retinol levels were 1.7 to 11.4 micrograms/ml in silicone oil and 2.4 to 7.3 micrograms/ml in fluorosilicone oil; the cholesterol levels were 2.7 to 12.6 micrograms/ml in silicone oil and 7.5 to 15.6 micrograms/ml in fluorosilicone oil. Fluorosilicone and silicone oils (1000 cs) removed from human eyes at 7.3 and 102.0 weeks postoperatively had a retinol content of 5.4 and 2.9 micrograms/ml, respectively. Silicone oil of 1000 cs removed from a patient 51 weeks postoperatively and silicone oil of 12,500 cs removed 96 weeks postoperatively gave reaction characteristics for cholesterol, 230 and 99 micrograms/ml, respectively.     

兔玻璃体内注射聚N-异丙基丙烯酰胺-聚氧化乙烯纳米粒的眼内毒理学效应

目的:评估玻璃体腔内注射新型缓释给药载体聚N-异丙基丙烯酰胺-聚氧化乙烯(PNIPAAm-PEO)纳米粒的眼内毒理学效应。方法:玻璃体腔注射不同浓度(1mg/0.1mL,2mg/0.1mL,3mg/0.1mL,4mg/0.1mL)的PNIPAAm-PEO纳米稀释液后于不同时间点行裂隙灯、检眼镜、视网膜电图以及组织病理学检测。对照组注射0.1mL无菌生理盐水。将所用不同浓度稀释液局部点眼,观察局部组织的刺激反应。结果:兔眼角结膜对检测浓度范围内的PNIPAAm-PEO有良好耐受性,眼部无刺激症状。玻璃体腔内注射1mg和2mg组未见明显视网膜毒性反应。3mg组眼底检查无异常,ERG-b波1~3d下降幅度>30%,第7~14d略有恢复;第14d光镜下视网膜部分感光细胞外节间隙增宽,外丛状层以内结构空泡变性,细胞排列正常;电镜下各层均有较明显的结构改变,广泛的细胞水肿和空泡变性,细胞间隙增宽,感光细胞膜盘结构基本正常。4mg组ERG-b波波幅下降>30%;第1~14d组织病理学观察均有明显视网膜结构破坏,广泛空泡变性,部分感光细胞的盘膜崩解,层状结构紊乱、模糊不清。结论:PNIPAAm-PEO纳米粒的眼部耐受性良好,具有用作眼部给药载体的潜力,但大剂量使用时应注意眼部安全性问题。     

Retinal toxicity of intravitreal ganciclovir in rabbit eyes following vitrectomy and insertion of silicone oil

BACKGROUND: Although intravitreal ganciclovir dosages up to 500 microg have been demonstrated to be safe in some studies, other studies have shown toxic retinal effects in rabbit eyes without silicone oil at lower dosages. In current clinical practice, the same dosage of intravitreal antiviral agent is given regardless of whether there has been retinal detachment repair with silicone oil. We performed a study to investigate, in rabbit eyes following vitrectomy and silicone oil insertion, the retinal toxicity of serial intravitreal injections of ganciclovir, using dosages previously found not to produce significant toxic effects in nonvitrectomized eyes. METHODS: Twenty-eight eyes of 14 New Zealand pigmented rabbits underwent pars plana vitrectomy and silicone oil insertion. One eye of each animal received an intravitreal ganciclovir injection twice weekly for 2 weeks.The other eye received 0.1 mL of normal saline as a control. Three dosages of ganciclovir (50, 100 or 200 microg/0.1 mL) were used in three groups of three to six animals. Scotopic electroretinography and histologic examination were performed 2 weeks postoperatively. RESULTS: No differences in scotopic b-wave threshold (p = 0.23, 0.78 and 0.50 for ganciclovir dosages of 50, 100 and 200 microg/0.1 mL respectively, Mann-Whitney U test) or in light microscopy findings were noted between the treatment and control eyes at any dosage of ganciclovir. Surgical complications were observed in eight eyes; the data for these eyes were not used for analysis. INTERPRETATION: Ganciclovir dosages of up to 200 microg/0.1 mL appear to be safe for serial intravitreal injection in rabbit eyes following vitrectomy and silicone oil insertion.     

Experiment Study of Retinal Ultrastructure after Intravitreal FK506

Purpose : To investigate the retinal toxicity of FK506 by intravitreal administration.Methods:Twenty-two eyes of 14 New Zealand rabbits were investigated. FK506 at concentrations of 5,25 and 50μg/eye was injected into the vitreous cavities respectively.The control eyes were received mixed solution of balanced salt and ethanol. All eyes were examined by tonometry, slit lamp and indirect ophthalmoscopy preoperatively and postoperatively at the 1^st, 3^rd, 7^th, and 14^th day respectively. In the final examination, all eyes were enucleated and processed for light and electron microscopy.Results: No evidence of toxic reaction was seen in the eyes received 25μg FK506 or less of FK506. Several eyes received 50μg FK506 and control eyes developed conjunctival congestion and slightly bloody exudates in anterior chamber which may be related to irritation of ethanol. Two of five eyes received 50μg developed transient vitreous opacities.Electron microscopically, the mitochondria of the photoreceptor cells were swelled in the eyes treated with 50μg FK506.Conclusion : It is safety with intravitreal FK506. There are no irritation and toxicity to the rabbits eyes with the intravitreal doses of 251.zg FK506 or less. The doses of 50μg FK506 are proved to be toxic to the retina.     

Intravitreal acetylsalicylic acid in silicone oil: pharmacokinetics and evaluation of its safety by ERG and histology

BACKGROUND: A new method of intravitreal drug delivery of acetylsalicyclic acid (AS) in silicone oil was investigated for safety and for its pharmacokinetics in the posterior pole of the eye. METHODS: The AS was mixed in silicone oil to a concentration of 1.67 mg/ml. After vitrectomy, 15 NZW rabbits received an intravitreal injection of AS/silicone oil suspension. Clinical examination, pre- and postoperative electroretinography (ERG) and histology were performed. The pharmacokinetics of the distribution of salicylic acid was determined by HPLC analysis at 6 h, 24 h and 5 days in optic nerve, retina, choroid, vitreous, and blood. RESULTS: Clinical examination and histology revealed no adverse effects or signs of toxicity. The ERGs showed no significant difference between the pre- and postoperative results. The salicylic acid concentrations demonstrated peak values in the residual vitreous (640.0 micrograms/ml), choroid (446.0 ng/mg) and retina (281.3 ng/mg) at 6 h. At 24 h, the salicylic acid concentration decreased to 20.9 micrograms/ml in the residual vitreous and to 38.5 ng/mg in the retina. At 5 days the retinal level was still 48.1 ng/mg. CONCLUSIONS: AS delivery by intravitreal administration of loaded silicone oil is a safe method and results in high concentrations of salicylic acid in the posterior segment of the eye while maintaining low blood levels.     

Experimental retinal tolerance to very low viscosity silicone oil (100 cs) as a vitreous substitute compared to higher viscosity silicone oil (5000 cs)

We evaluated the toxicity of very low viscosity (100 centistokes) and higher viscosity silicone oil (5000 centistokes) in rabbit eyes as a short-to-long-term postoperative vitreous substitute (6 weeks to 5 months). Emulsification of 100-cs and 5000-cs silicone oil did not occur in eyes which were followed for as long as 5 months. No toxic effects to retinal cells were detected by light or electron microscopy. Because no toxic effects were seen with 100-cs silicone oil, it can be used in an outpatient setting as a short-term postoperative tamponading agent. Electroretinographic responses of silicone-injected eyes were normal.     

抗血管内皮生长因子bevacizumab兔眼玻璃体腔重复注射的安全性研究

目的　观察抗血管内皮生长因子bevacizumab（商品名Avastin）兔眼玻璃体腔重复注射的眼内安全性。方法 14只青紫兰兔分为3组,其中12只兔的右眼设为实验组,左眼设为实验对照组,2只兔为正常对照组。实验组右眼予以25 mg/ml的bevacizumab玻璃体腔注射,实验组根据不同注射剂量分为2.5、5.0 mg 2个剂量组,左眼分别注射等剂量0.9%生理盐水作为实验对照。玻璃体腔共注射3次,每次间隔2周。每次注射前、注射后2 d,第3次注射后1、4周采用裂隙灯显微镜、+90 D前置镜、B型超声、超生生物显微镜（UBM）、光相干断层扫描（OCT）进行临床指标观察,视网膜电图（ERG）和闪光视觉诱发电位（F-VEP）进行视网膜功能检测。第3次注射完毕后1、4周分别摘取眼球进行病理组织学观察和凋亡细胞检测。结果　所有实验眼和实验对照眼均未见明显炎症反应,各组眼底未见明显异常,玻璃体无混浊、出血。B型超声、UBM和OCT检查均未见明显改变。注射前后不同剂量实验组与实验对照组、正常对照组眼压、前房闪辉计数比较,差异均无统计学意义(P＞0.05)。不同剂量实验组与注射前、实验对照组、正常对照组最大反应ERG a、b波比较,差异均无统计学意义(P＞0.05)。注射前后,F-VEP N₁波潜伏期和P1波振幅各组差异均无统计学意义(P＞0.05)。光学显微镜观察发现,不同剂量实验组第3次注射后1 周玻璃体腔可见少量炎症细胞,注射后第4周未见炎症细胞;实验对照组和正常对照组注射前后视网膜组织形态未见明显改变。5.0  mg实验组第3次注射后1周电子显微镜下可见炎症细胞,个别视细胞细胞核呈空泡样改变,其余未见明显异常。凋亡细胞计数显示,第3次注射后1周,5.0 mg实验组与2.5、5.0 mg实验对照组（Z=0.227）和正常对照组（Z=1.341）组间凋亡细胞数量比较,差异均有统计学意义（P＜0.01）,第3次注射后4周,各组差异无统计学意义（χ2=4.826,P>0.05）。结论　5.0 mg bevacizumab在兔眼玻璃体腔多次注射视网膜有一定轻微毒性反应。     

眼内硅油取出术前激光光凝对防止视网膜脱离复发的效果观察

目的：观察视网膜脱离手术硅油填塞患眼在取出硅油前进行视网膜光凝对防止视网膜再脱离的效果。 方法：对24例24只施行过玻璃体视网膜手术和硅油填塞的视网膜脱离患眼,在取出硅油前2周至3个月时用氩绿或氪红激光在巩膜嵴后作全周或半周播散性光凝。硅油在注入后4～27个月(平均10.6个月)时取出。 结果：22只眼硅油取出后视网膜保持复位,占91.7%;2只眼分别因周边部原裂孔处附着不牢及前PVR发生视网膜再脱离,占8.3%。 结论：视网膜脱离手术硅油填塞患眼,取硅油前先行激光光凝,可减少硅油取出后视甲膜脱离的复发. （中华眼底病杂志,1997,13：197-198）