琥珀酸甲泼尼龙兔眼球周注射的药代动力学研究

目的：检测琥珀酸甲泼尼龙(methylprednisolone sodium succinate,MPS)兔眼球周注射后,MPS和其在眼内的代谢产物甲泼尼龙(methylprednisolone,MP)的分布及药代动力学情况。

方法：兔眼球周注射琥珀酸甲泼尼龙钠10mg,采用质谱-液相色谱方法检测MPS和MP在巩膜、脉络膜和视网膜、玻璃体、虹膜、房水、晶状体、视神经和血浆中的浓度。

结果：球周注射琥珀酸甲泼尼龙钠后, MPS浓度在眼内组织中的达峰时间为注药后0.25～1h,在血浆中的达峰时间为注药后0.25h; MP浓度在眼内组织中的达峰时间为0.5～6h,在血浆中的达峰时间为注药后0.5h。MPS和MP在眼内各组织的达峰浓度由高到低依次为巩膜、视神经、脉络膜和视网膜、虹膜、晶状体,二者在晶状体内的浓度均为所有眼部组织中最低,且远远低于眼内其它组织的含量,但平均驻留时间最长。

结论：球周注射MPS是一种有效的向眼组织传递药物的方式,且该药在眼内的分布有利于向巩膜、视神经和脉络膜视网膜给药,而不易被晶状体吸收。     

玻璃体腔注射万古霉素和蛇毒降纤酶治疗兔眼球穿通伤并发症的效果

目的:观察玻璃体腔注射蛇毒降纤酶和万古霉素对外伤性增生性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)的抑制效果.方法:新西兰白兔40只右眼建立外伤性出血性眼球穿通伤动物模型.左眼为空白对照眼.随机分为4组,生理盐水组10眼,玻璃体腔注射生理盐水0.1mL;蛇毒降纤酶组10眼,玻璃体腔注射蛇毒降纤酶0.1U(0.1mL);万古霉素组10眼,玻璃体腔注射万古霉素1mg(0.1mL);联合用药10眼,玻璃体腔分别注射蛇毒降纤酶0.1 U及万古霉素1mg.通过裂隙灯显微镜观察眼前节炎症情况,眼前节炎症持续超过2wk以上者行玻璃体腔微生物学培养;直接眼底镜观察玻璃体出血指数、外伤性PVR情况.结果:联合用药组玻璃体出血指数低于生理盐水组(P<0.01)、外伤性PVR程度低于生理盐水组(P<0.01);联合用药组玻璃体出血指数低于万古霉素组(P<0.05)、外伤性PVR程度低于万古霉素组(P<0.01);生理盐水组、蛇毒降纤酶组各发生细菌性眼内炎3例(30%);万古霉素组、联合用药组未见细菌性眼内炎的发生.结论:在外伤性出血性眼球穿通伤动物模型中,玻璃体腔注射蛇毒降纤酶和万古霉素可能可以促进玻璃体腔出血的吸收、降低外伤性PVR程度和减低感染性眼内炎症发生率.     

兔眼玻璃体腔注射替考拉宁眼内药代动力学研究

背景 眼内炎是严重的感染性眼病,早期有效的药物治疗至关重要.替考拉宁眼内用药治疗眼内炎及眼内药代动力学方面的研究文献报道较少.目的 探讨兔眼玻璃体腔注射替考拉宁眼内药代动力学过程及特点.方法 取日本大耳白兔33只,右眼玻璃体腔注射替考拉宁0.5 mg后,分别于15 min、30 min和1、2、4、6、12、24、48、96、192 h抽取玻璃体及房水各0.1ml,采用微生物检定法测定替考拉宁的质量浓度.结果 替考拉宁标准品质量浓度的对数值随着抑菌圈直径的增加而增加,其标准品回归曲线方程:Y=0.174X-0.813(R2 =0.999),在替考拉宁质量浓度为1.0-80.0 mg/L范围内线性关系良好.替考拉宁玻璃体腔单次注射符合开放性二室模型,玻璃体腔分布相Tα1/2与消除相Tβ1/2分别为1.68 h、152.15 h,房水中分布相T1/2与消除相Tβ1/2分别为2.83 h、70.56h.替考拉宁在玻璃体、房水中的峰质量浓度分别为(358.47±21.53)mg/L、(102.17±9.54)mg/L,达峰时间分别为1h;在192 h时,玻璃体、房水中替考拉宁质量浓度分别为(4.38±0.68)mg/L、(2.38±0.38)mg/L.结论 替考拉宁0.50 mg玻璃体腔注射后能在玻璃体、房水中维持较长时间的药物治疗质量浓度.     

玻璃体腔注射曲安奈德和万古霉素防治眼球穿通伤并发症实验研究

目的 外伤性增生性玻璃体视网膜病变(proliferative vitreoretinopathy.PVR)和细菌性眼内炎是眼球穿通伤常见的并发症.在外伤性出血性眼球穿通伤动物模型中,观察玻璃体腔注射曲安奈德和万古霉袭对眼内炎症、感染及外伤性PVR的抑制效果.方法 建立外伤性出血性眼球穿通伤动物模型.随机分为生珲盐水组、曲安奈德组、万古霉素组、联合用药(曲安奈德+万古霉素)组四组.通过裂隙灯显微镜观察眼前节炎症情况,眼前节炎症2级以卜且持续超过1周以上者行玻璃体腔微生物学培养;直接眼底镜观察外伤性PVR情况.结果 联合用药组外伤性PVR程度、眼前节炎症程度都低于生理盐水组、万古霉索组;生理盐水组、曲安奈德组各发生细菌性眼内炎2例(20%);万古霉素组、联合用药组未见细菌性眼内炎的发生.结论 在外伤性出血性眼球穿通伤动物模型中,玻璃体腔注射曲安奈德和万古霉索能降低外伤性PVR程度和减低眼内炎症、感染的发生率.     

合并脉络膜脱离的裂孔性视网膜脱离曲安奈德玻璃体腔注射的疗效评价

目的通过曲安奈德玻璃体腔注射寻求治疗合并脉络膜脱离的裂孔性视网膜脱离的有效方法。方法对19例(19只眼)合并脉络膜脱离的裂孔性视网膜脱离,给予曲安奈德玻璃体腔注射4mg,并对病人症状、眼压、手术条件的改善以及术后增殖性玻璃体视网膜病变的发生进行观察。结果曲安奈德成功注入18只眼的玻璃体腔,1只眼误入脉络膜上腔。注药后所有患者的症状都有缓解;前房闪辉、浮游细胞及玻璃体情况改善;17只眼眼压回升,UBM检查脉络膜、睫状体复位;2只眼眼压不升,UBM检查脉络膜、睫状体未能复位;视网膜复位手术一次性成功17只眼(89.5%),2只眼需行二次手术。随访2个月至13个月,18只眼视网膜复位。1只眼发生增殖性玻璃体视网膜病变需再次手术治疗。结论曲安奈德玻璃体腔注射能迅速减轻患者症状,对合并脉络膜脱离的裂孔性视网膜脱离的治疗及预后的改善具有积极的辅助作用。     

气相色谱法测定γ—榄香烯在兔眼内的分布

目的 测定正常兔眼球后注射榄香烯后药物在眼内的分布。方法 采用气相色谱法测定正常兔眼单次及连续１周球后注射榄香烯后房水、玻璃体、视网膜和脉络膜中β－榄香烯后１ｈ,房水、玻璃体、视网膜和脉络膜中均检测到β－榄香烯。连续１周注射后,仅视网膜和脉络膜中检测到β－榄香烯,浓度与单次注射相比无明显增加。结论 正常兔眼球后注射榄香烯可通过血－视网膜屏障进入眼内,连续用药后无明显蓄积作用。     

气相色谱法测定β-榄香烯在兔眼内的分布

目的测定正常兔眼球后注射榄香烯后药物在眼内的分布。方法采用气相色谱法测定正常兔眼单次及连续１周球后注射榄香烯后房水、玻璃体、视网膜和脉络膜中β－榄香烯的浓度。结果单次球后注射榄香烯后１ｈ，房水、玻璃体、视网膜和脉络膜中均检测到β－榄香烯。连续１周注射后，仅视网膜和脉络膜中检测到β－榄香烯，浓度与单次注射相比无明显增加。结论正常兔眼球后注射榄香烯可通过血－视网膜屏障进入眼内，连续用药后无明显蓄积作用。     

纤溶酶K区缺失突变体玻璃体腔注射对光化学诱导大鼠视网膜分支静脉阻塞的溶栓作用

背景 视网膜静脉阻塞是常见的视网膜血管性疾病,目前溶栓和抗凝疗法是重要的治疗手段.然而,系统溶栓疗法效率较低,且易增加出血风险. 目的 观察玻璃体腔注射纤溶酶K区缺失突变体(PLM-ΔK)对光化学诱导的大鼠视网膜分支静脉阻塞(BRVO)的治疗作用. 方法 用SD大鼠尾静脉注射孟加拉玫瑰红溶液40 mg/kg,然后用氩激光照射视网膜静脉法建立SD大鼠BRVO模型,采用随机数字表法将造模成功的40只大鼠随机分为平衡盐溶液(BSS)组、0.01U(商品单位)PLM-ΔK组、0.02 U PLM-ΔK组和0.03 UPLM-ΔK组,每组10只.造模并避光饲养大鼠12h后于大鼠玻璃体腔内分别注射BSS和0.01、0.02或0.03 UPLM-ΔK 10μl,各组大鼠于注射后3d行间接检眼镜、荧光素眼底血管造影(FFA)检查.用过量麻醉法处死SD大鼠并制备视网膜铺片和眼球壁切片,采用苏木精-伊红染色法观察大鼠球壁的形态学变化;采用免疫荧光法检测大鼠球壁组织中人纤连蛋白(FN)和层黏连蛋白(LN)的表达;透射电子显微镜下观察大鼠视网膜的超微结构改变.结果 玻璃体腔内药物注射后3d,FFA显示BSS组及0.01、0.02或0.03 U PLM-ΔK组视网膜分支静脉再通达2支以上的大鼠数量分别为0、3、6和8只,组间总体比较差异有统计学意义(x2=9.635,P=0.022),其中0.01 U PLM-ΔK组再通血管的大鼠数量与BSS组比较,差异无统计学意义(Z=-1.558,P=0.119),而0.03 U PLM-ΔK组再通血管的大鼠数量明显多于0.01 U PLM-ΔK组,差异有统计学意义(Z=-2.762,P=0.006).玻璃体腔药物注射后3d,BSS组大鼠视网膜静脉内可见血栓形成,视网膜铺片可见新生血管;而0.03 U PLM-ΔK组可见大鼠玻璃体后脱离,视网膜铺片未见新生血管形成.BSS组可见FN主要表达于内界膜(ILM)层、感光细胞层(PCL)、外界膜(OLM)层、脉络膜和巩膜,LN主要表达于大鼠ILM层、OLM层和巩膜,且均呈强表达.0.03 U PLM-ΔK组大鼠球壁各层组织中FN荧光强度较BSS组明显减弱,脉络膜层FN表达接近消失,LN在ILM层表达增强,而OLM层和巩膜表达减弱.结论 玻璃体腔注射PLM-ΔK促进阻塞的视网膜分支静脉再通,是潜在的BRVO治疗药物.PLM-ΔK玻璃体腔注射后可以扩散至脉络膜并降解FN和LN.     

曲安奈德玻璃体腔注射治疗脉络膜脱离型视网膜脱离的初步研究

目的探讨玻璃体腔注射曲安奈德治疗脉络膜脱离型视网膜脱离的疗效及安全性。方法选择未经有效治疗的脉络膜脱离型视网膜脱离患者,于手术前经睫状体平坦部向玻璃体腔内注入曲安奈德混悬液0．1ml(4mg),注药后观察葡萄膜炎反应及脉络膜脱离消失情况,并于5—10d后行视网膜脱离复位手术。结果有葡萄膜炎反应的13只眼其症状均不同程度减轻,裂孔检出率由注药前的2／13只眼提高至注药后的7／13只眼,绝大多数脉络膜脱离眼于注药后10d内消失,5只眼采用巩膜扣带术,6只眼采用玻璃体切除联合眼内填充术,2例患者放弃手术治疗。手术后平均随访4．45个月,接受手术者最终视网膜全部复位,无1例出现全身应用糖皮质激素的副作用。结论玻璃体腔注射曲安奈德能迅速、安全、有效地治疗脉络膜脱离型视网膜脱离,减轻葡萄膜炎反应,提高脉络膜脱离型视网膜脱离的手术复位率。(中华眼科杂志,2005,41：606-609)     

曲安奈德兔眼内注射治疗金黄色葡萄球菌眼内炎的有效性

目的:正确评价曲安奈德作为金黄色葡萄球菌性眼内炎辅助治疗的有效性。方法:30只健康青紫蓝兔所有右眼玻璃体腔注射ATCC25923标准金黄色葡萄菌104CFU/0.1mL混悬液,0.1mL建立眼内炎模型。建立眼内炎模型后24h,随机将实验动物分为3组,每组10眼进行不同干预,A(空白对照)组、B(玻璃体腔万古霉素)组、C(玻璃体腔万古霉素 曲安奈德混悬剂)组。干预后每日间接眼底镜观察结膜、角膜、前房、虹膜、玻璃体的变化并按照规定的时间进行临床炎症评分;注射细菌后24h及干预后14d所有实验动物行B超检查;干预后5d进行玻璃体腔细菌学培养;干预14d后处死所有动物行光镜检查并进行病理评分。结果:B,C组较A组炎症明显减轻。不同时间3组进行临床炎症评分,A组评分明显高于B,C2组,A,B,C3组间评分均有显著性差异(P<0.05),5,7,14d验证评分B,C2组间均无显著性差异(P=0.717,0.694,0.543);7,14d前房闪辉分级B,C组间无显著性差异(P=0.796,0.562);A,B,C3组间细菌学培养检出率无统计学意义;B超显示A,B,C3组视网膜脱离发生率无显著性差异(P=0.830);光镜下见A组各组织结构均失去正常形态不易辨认;B、C组组织结构能够辨认。对角膜、前房、玻璃体、视网膜进行病理评分,A,B,C3组间有显著性差异(P=0.000),组间比较B,C视网膜分级有显著性差异(P=0.011),其余均无显著性差异。结论:金黄色葡萄球菌性眼内炎治疗中玻璃体腔注射曲安奈德对眼组织的保护作用具有局限性。     

Clearance of intravitreal voriconazole

Purpose To investigate the elimination rate of voriconazole after intravitreal injection in rabbits. METHODS: Intravitreal injections of 35 microg/0.1 mL voriconazole were administered to rabbits. Vitreous and aqueous humor levels of voriconazole were determined at selected time intervals (1, 2, 4, 8, 16, 24, and 48 hours), and the in vitreous half-life was calculated. Four to six eyes per time point after injection were enucleated and immediately stored at -80 degrees C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals. Voriconazole concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography (HPLC). RESULTS: The concentration of intravitreal voriconazole at various time points exhibited exponential decay with a half-life of 2.5 hours. The mean vitreous concentration was 18.912 +/- 2.058 microg/mL 1 hour after intravitreal injection; this declined to 0.292 +/- 0.090 microg/mL at 16 hours. The mean aqueous concentration was much lower and showed a decline from 0.240 +/- 0.051 microg/mL at 1 hour to undetectable levels 8 hours after injection. CONCLUSIONS: Vitreous concentrations achieved during the first 8 hours were greater than the previously reported minimum inhibitory concentrations (MICs) of organisms most involved in fungal endophthalmitis. A rapid decline of intravitreal concentration suggests that supplementation of intraocular voriconazole to maintain therapeutic levels may therefore be required in clinical settings. Further studies are needed to determine the elimination rate of voriconazole after intravitreal injection in humans.     

周边视网膜冷冻联合tPA和C3F8玻璃体腔注射诱导玻璃体后脱离的动物实验研究

目的探讨周边视网膜冷冻后玻璃体腔注射酶或/和膨胀气体诱导玻璃体后脱离（Posterior vitreous detachment,PVD）的效果、机制并观察其对视网膜的毒性作用。方法选用新西兰白兔48只,随机分为实验组和对照组。实验组I行周边视网膜冷冻及玻璃体腔内注射纤维蛋白溶解酶原激活剂（tissue plasminogen activator,tPA）,实验组Ⅱ玻璃体腔单纯注射C3F80.3ml,实验组Ⅲ行周边视网膜冷冻,24小时后注射tPA25μg和C3F80.3ml。记录各实验组产生玻璃体后脱离的时间并观察眼内的反应性变化,最后行光镜和扫描电镜检查,观察各实验组用药后的组织形态学变化。结果三组均有效诱导PVD,组间两两比较差异有显著性（〈0.05）,实验组Ⅰ和Ⅱ眼内反应较轻,实验组Ⅲ反应最重,并有视网膜结构及功能损害。结论周边视网膜冷冻后tPA注射是诱导玻璃体后脱离安全有效的方法。单纯膨胀气体注射并非真正意义的玻璃体后脱离。酶与气体联合用药可缩短玻璃体后脱离产生时间,但容易造成视网膜药物毒性变化。     

Intravitreal erythromycin in the treatment of induced staphylococcal endophthalmitis.

Intravitreal injection of 500 mcg of erythromycin as the gluceptate caused no toxicity to ocular structures. This dose maintained bacterial inhibitory concentrations in the vitreous for up to 24 hours. Consistent aqueous levels were not obtained with intravitreal injection. Intravitreal treatment of Staphylococcus aureus endophthalmitis was successful in 11 of 13 rabbit eyes compared to 2 of 13 treated with subconjunctival erythromycin.     

万古霉素在正常兔眼和细菌性眼内炎兔眼内的药代动力学研究

背景万古霉素近年来常被作为金黄色葡萄球菌性眼内炎治疗的首选药物,万古霉素在眼内药代动力学的研究报道较少。目的观察万古霉素在正常兔眼和细菌性眼内炎兔眼房水、玻璃体及血清中质量浓度的变化,并进行药代动力学参数比较。方法选取健康成年兔72只,采用随机数字表法分为正常组和眼内炎组,每组36只。眼内炎组兔右眼玻璃体腔内接种2000CFU／ml金黄色葡萄球菌建立眼内炎模型,注射后72h待出现典型的眼内炎表现时,兔眼玻璃体腔内注射10g／L万古霉素注射液0．1ml,分别于注射后0．5、2、4、6、12、24、48、72、84h经兔耳缘静脉采血2ml,之后以空气栓塞法处死动物,摘除眼球,收集房水和玻璃体,利用高效液相色谱仪紫外（HPLC—UV）法检测万古霉素在血液、房水和玻璃体内的质量浓度。3p97药代动力学软件拟合药代动力学参数。结果HPLC法的准确度和精确度符合生物样品的检测要求。玻璃体腔内注射万古霉素后,其在正常兔眼内的代谢呈二室模型,拟合曲线的高峰质量浓度Cmax分别为50．16mg／L和751．42mg／L,t1/2为51．04h和53．21h;其在金黄色葡萄球菌性眼内炎兔眼中代谢呈一室模型,高峰质量浓度Cmax分别为24．94mg／L和687．66mg／L,t1/2分别为11．42h和12．91h,2组动物血药质量浓度均较低,差异无统计学意义（P〉0．05）。正常组和眼内炎组玻璃体腔内注射万古霉素后随时间延长,玻璃体中万古霉素的质量浓度逐渐下降,而房水中出现先升高后下降的趋势。与正常组相应时间点比较,眼内炎组玻璃体和房水中万古霉素的质量浓度均明显下降,差异均有统计学意义（P〈0．05,P〈0．01）。结论HPLC能满足万古霉素药代动力学分析的需要;万古霉素在正常兔眼内的质量浓度较高,清除缓慢,而在细菌性眼内炎兔眼中质量浓度较低、清除较快。     

Dispase诱发兔眼玻璃体后脱离的效果和安全性评价

目的 采用Dispase在兔眼中诱导完全性PVD形成，评价其效果和安全性。方法 选择健康成年的青紫蓝兔30只，随机分成5组，采用玻璃体内注射，分别注射Dispase0.005U,0.0125U(2组），0.025U,0.05U/0.05ml,PBS0.05ml注射到另一只内作为对照。术前术后眼底镜，裂隙灯和VOLK 90D随访观察。并进行B超和视网膜电图（ERG）检查，最后取眼球对视网膜进行扫描电镜和透射电镜观察。结果 注射Dispase≥0.0125U可见玻璃体后脱离，部分伴有不同程度的眼底出血：B型超声检查见玻璃体混浊和后脱离；术后电生理检查，0.005U和0.0125U组ERG没有变化，≥0.025U，部分出现ERG振幅下降；对照组没有以上改变。结论 Dispase0.0125U可以在兔眼中成功，安全诱发完全性玻璃体后脱离（PVD），更大剂量同样有效。但是有一定毒性作用。     

Vitreous prolapse and IOL dislocation during intravitreal injection of triamcinolone acetonide

Background To report on procedure-related anterior segment complications during intravitreal injections.Methods In a prospective interventional case series, 614 eyes received a total of 723 intravitreal injections of about 20 mg triamcinolone acetonide (in 0.2 ml) after paracentesis and aqueous humor drainage for various indications.Results In three eyes (0.49% of all eyes) a vitreous prolapse occurred during the injection. In one eye, the vitreous prolapse was combined with dislocation of the intraocular lens (IOL). All three eyes were pseudophakic, showing an posterior capsule defect, and the IOL located in the ciliary sulcus. They were treated by translimbal vitrectomy, and one eye with reposition of the IOL. No other procedure-related postoperative complications were observed during injection or follow-up (7.8±7.1 months).Conclusions Intravitreal injections may cause a vitreous prolapse into the anterior chamber with or without IOL decentration or dislocation in predisposed eyes. Ophthalmologists should be aware of this possible complication and inform patients at risk.None of the authors received any financial support, or had any financial interest.     

Induction of posterior vitreous detachment in rabbits by intravitreal injection of tissue plasminogen activator following cryopexy

The purpose of this study was to generate intravitreal plasmin after intravitreal injection of tissue plasminogen activator (TPA) and cryopexy, and to assess its proteolytic effect on the vitreoretinal border region.Twenty-four hr after a mild cryopexy, 25 microg recombinant tissue plasminogen activator (TPA) was injected into the vitreous cavity, the fellow eye received an intravitreal injection of the same volume of buffered salt solution. Light, scanning and transmission electron microscopy was performed in 24 eyes that underwent vitrectomy 1 week later. Plasmin was measured prior and 2 hr after intravitreal TPA injection (4 eyes). Hyaluronic acid (8 eyes) and vitronectin (4 eyes) were measured 1 week after TPA- or BSS-injection and compared to untreated controls.In all eyes treated with TPA, histopathologic examination by scanning and transmission electron microscopy demonstrated a complete detachment of the vitreous from the surface of the retina as well as from the posterior surface of the lens. After BSS-injection, vitreous cortex attachment to the retina was demonstrated in all eyes. Two hr after TPA-injection, plasmin increased to 9.75 mU ml(-1)(s.d.+/-2.3). Neither a decrease of hyaluronic acid nor an increase of transglutaminase, that might alter the vitreous structure leading to a collapse of the vitreous, were detected in treated eyes. There was no increase of vitronectin indicating proliferative activity.A temporary breakdown of the blood-retinal barrier by cryopexy combined with intravitreal injection of TPA is a sufficient technique to induce a posterior vitreous detachment enzymatically. The method may be useful prior to mechanical vitrectomy.     

Intravitreal concentration and clearance of triamcinolone acetonide in nonvitrectomized human eyes

PURPOSE: To determine the intravitreal concentration and clearance of triamcinolone acetonide at various intervals after intravitreal injection into nonvitrectomized eyes. METHODS: Six participants were administered 4 mg (0.1 cc) of triamcinolone acetonide ophthalmic suspension. All six eyes underwent therapeutic pars plana vitrectomy with membranectomy at various post injection intervals ranging from 1.25 to 5 months from the intravitreal injection. Undiluted specimens of vitreous overlying the macula and of aqueous humor were submitted for analysis. Vitreous and aqueous humor concentrations of triamcinolone were measured by high performance liquid chromatography. RESULTS: Four eyes demonstrated detectable intravitreal concentrations of triamcinolone acetonide between 1.25 and 2.75 months after a single injection. Two eyes had an undetectable level of triamcinolone in both the vitreous and aqueous at 3 and 5 months post single injection. CONCLUSIONS: The intravitreal concentration of triamcinolone acetonide is detectable up to 2.75 months post a single 4 mg injection in nonvitrectomized eyes. A reinjection interval of 3 months may be needed to achieve sustained measurable levels of triamcinolone in nonvitrectomized patients.     

Ocular toxicity of intravitreal clarithromycin.

OBJECTIVE: To investigate the ocular toxicity and clearance of intravitreal clarithromycin lactobionate (Klaricid) and to determine the highest nontoxic dose. MATERIALS AND METHODS: To evaluate toxicity, 24 New Zealand white rabbits were divided into six groups (four rabbits each). Rabbits were examined preoperatively and electroretinography (ERG) was performed. The left eyes of the animals served as controls and received intravitreal injection of 0.1 mL sterile water. Klaricid (0.1 mL) was injected into the midvitreous cavity of the right eyes at concentrations of 25 microg, 250 microg, 500 microg, 1.0 mg, 2.0 mg, and 4.0 mg/0.1 mL. The animals were followed up to 15 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy. Ten New Zealand rabbits were used for the vitreous clearance study as drug test rabbits and two additional rabbits were used to generate control retina and vitreous. The highest nontoxic dose (1 mg) was injected into the vitreous and the concentration of clarithromycin in the vitreous was determined using high-performance liquid chromatography at various time intervals after injection. RESULTS: Cataract occurred after intravitreal doses of 2.0 and 4.0 mg. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 4.0-mg group; it was normal in other groups. Histopathologic sections showed localized retinal necrosis and disorganization with the 2.0 and 4.0 mg dosage. No histologic changes were found in the other groups. The half-life of intravitreal clarithromycin was found to be 2 hours. No metabolites of clarithromycin were observed in the vitreous samples. CONCLUSION: Intravitreal clarithromycin lactobionate is nontoxic to rabbit eyes up to a dose of 1.0 mg. Because of its broad-spectrum antibiotic effect and appropriate half-life in the vitreous, it may be a good choice for intravitreal treatment of susceptible organisms.