丁胺卡那霉素地塞米松复方脂质体在兔眼玻璃体内的药代动 …

应用丁胺卡那霉素地塞米松复方脂质体玻璃体内注射以延长两种药物的半衰期。方法大白兔随机分４组，正常眼２组和眼内炎眼２组均分别注射复方脂质体和游离药物。结果丁卡在正常眼复方脂质体的半衰期较游离药物延长１．８倍，在眼内炎眼延长３．４倍。     

丁胺卡那霉素地塞米松复方脂质体的眼毒性研究

为探讨治疗细菌性眼内炎的新型制剂丁胺卡那霉素地塞米松复方脂质体的视网膜毒性,将２０只新西兰白兔随机分为四组,第一、二、三组分别于玻璃体内注射不同剂量的丁卡地塞复方脂质体,第四组玻璃体内注入注射用水作对照。术后行裂隙灯、检眼镜活体检查,并行ＥＲＧ检查和视网膜透射电镜检查。结果：含丁卡６００μｇ、地塞米松５２５μｇ的０．１５ｍｌ复方脂质体对视网膜无明显毒性,而含丁卡８００μｇ、地塞米松７００μｇ的复方脂质体则显示毒性反应。结论：丁卡地塞复方脂质体较游离药物毒性小、作用时间长,是一种治疗细菌性眼内炎的安全有效药物制剂     

丁胺卡那霉素在兔眼玻璃体内的药代动力学研究

用荧光偏振免疫法检测丁胺卡那霉素在家免正常眼、玻璃体切除和眼内炎等6种模型眼玻璃体中的药物动力学。结果表明丁胺卡那霉素在眼内的代谢速率在血-眼屏障和玻璃体受损后加快。从药物动力学的观点，玻璃体切除术用于轻度眼内炎会使眼内药物半衰期缩短．在重度眼内炎则能延长药物在眼内的停留时间。丁胺卡那霉索在眼内的吸收、分布和消除为一级动力学过程。 （中华眼底病杂志，1995，11：28-30）     

玻璃体切除联合两性霉素B脂质体球内注射治疗真菌性眼内炎

目的:探讨玻璃体切除联合两性霉素B脂质体眼内注药治疗真菌性眼内炎的疗效。方法:对34例(34眼)真菌性眼内炎采取玻璃体切除联合眼内注药治疗进行回顾性研究,观察其疗效。结果:34眼中有30眼视力均较术前提高,3例给予两性霉素B脂质体5μg两次前房注射,4眼感染复发行眼内容物摘出。结论:真菌性眼内炎的预后不佳。早期行玻璃体切除联合两性霉素B脂质体眼内注药,可挽救部分视力,是目前治疗真菌性眼内炎有效方法。     

去甲万古霉素兔眼眼内药代动力学研究

目的研究去甲万古霉素玻璃体注射和结膜下注射两种给药途径的兔眼眼内药代动力学,为临床治疗敏感菌引起的感染性眼病提供依据.方法健康成年白兔36只,随机分为玻璃体注射组和结膜下注射组,均注射1 mg去甲万古霉素.各组房水、玻璃体样品采用高效液相色谱法检测.结果玻璃体注射组在试验观察的48h内玻璃体及房水中药物浓度均高于大多数革兰氏阳性菌的最低抑菌浓度(minimal inhibitoryconcentration MIC).结膜下注射组在试验72 h内玻璃体中药物浓度低于MIC,房水中可达有效浓度.结论玻璃体注射1 mg去甲万古霉素可用于治疗感染性眼内炎,结膜下注射仅对眼前段感染有效,在眼后段不能达到治疗水平.(中国眼耳鼻喉科杂志,2005,5:347～349)     

微透析法检测万古霉素在兔眼玻璃体内的代谢

目的 利用微透析法联合高效液相色谱法连续、在线、活体检测万古霉素在兔眼玻璃体内的浓度,探讨微透析法在眼科活体药代动力学研究中的可行性.方法 将微透析探针植入兔眼玻璃体内24 h后,玻璃体内注射10 g·L-1万古霉素0.1 mL,利用微透析法直接采样,高效液相色谱法(HPLC-UV)连续检测30 min、1 h、2 h、4 h、6 h、12 h、24 h、48h、72 h和84 h正常兔眼和眼内炎兔眼玻璃体内万古霉素的浓度,并用计算机拟合并计算药代动力学参数.结果 正常免眼玻璃体内万古霉素的峰值浓度为(694.3±19.6)mg·L-1,半衰期为51.66 h;眼内炎兔眼玻璃体内万古霉素的峰值浓度为(721.4±29.4)mg·L-1,半衰期为11.91 h.所有的动物注药后84 h,玻璃体内万古霉素的浓度均高于最小抑菌浓度.结论 微透析法是活体检测玻璃体内药物浓度的有效、直接的方法,可以直接反映出药物浓度随时间的变化,具有较高的可行性.     

二性霉素B眼内缓释系统对白色念珠菌性眼内炎影响的实验研究

目的探讨二性霉素B眼内缓释系统对兔实验性白色念珠菌性眼内炎的治疗作用及其安全性。方法缓释系统由二性霉素B和乙交酯-丙交酯-己内酯三元共聚物（PGLC）制成。（1）药效学实验：50只新西兰兔右眼行中央部玻璃体切除,同时眼内注射10^4cfu／ml白色念珠菌悬液0．1ml,构建眼内炎模型后,随机数字表法分为5组,每组10只眼。A组,眼内炎对照组;B组,空白药物载体组;C组,二性霉素B眼液滴眼组;D组,二性霉素B眼内注射组;E组,二性霉素B眼内缓释系统组。对比观察各组眼内炎性反应。高效液相色谱分析方法定期检测眼内二性霉素B浓度。（2）毒性实验：20只正常新西兰兔分为3组：正常对照组,2只眼;DDS组,眼内植入1粒含药1mg的缓释系统,10只眼;空白载体组,眼内植入空白药物载体,8只眼。分别进行视网膜电图、眼部病理学及透射电镜检查,并行肝、肾病理学检查。结果E组在各个时间点玻璃体混浊较A、B、C组均明显减轻;E组与D组玻璃体混浊在2周内无差异,其后存在差异;D组玻璃体混浊在2周内与A、B、C组存在差异,但2周后无差异;C组在各个时间点玻璃体混浊较A、B组均无显著差异。眼内植入药物缓释系统后,视网膜电图无显著改变,视网膜病理学和电镜检查以及肝、肾病理学检查未见异常改变。结论二性霉素B眼内缓释系统能够抑制白色念珠菌性眼内炎进展。PGLC缓释系统释药稳定、安全、无毒性。（中华眼科杂志,2006,42：420-425）     

玻璃体内注射药物后行玻璃体切除治疗细菌性眼内炎

目的：探讨细菌性眼内炎的治疗方法。 方法：回顾分析细菌性眼内炎先玻璃体内注射药物后行玻璃体切除的23例(1组)与玻璃体切除同时注药的28例(Ⅱ组)的治疗效果。结果：两组治疗有效率相似，但显效率Ⅰ组为47.8%，Ⅱ组为17.9%；炎症控制所需的时间I组为10.3天，Ⅱ组为13.6天。均有显著差异(P<0.05)。Ⅱ组术后并发视网膜脱离的发生率是I组的3.3倍。 结论：玻璃体内先注射药物后切除治疗细菌性眼内炎，可增加玻璃体切除手术的安全性，提高眼内炎的治疗效果。 （中华眼底病杂志，1997，13：131-133）     

早期玻璃体内注射抗生素对玻璃体切除术治疗外因性眼内炎疗效的影响

目的探讨眼内炎的手术治疗方法及早期玻璃体内注射抗生素对玻璃体切除术治疗外因性眼内炎疗效的影响。设计回顾性病例对照研究。研究对象北京同仁医院2000年1月至2004年12月收治的外因性眼内炎患者94例(94眼)。方法全部患者均在确诊眼内炎后不同时间行常规三通道玻璃体切除术。其中46眼在发现眼内炎后先行玻璃体内注射抗生素,在注药后3-14天(平均5．6天)行玻璃体切除术(Ⅰ组),其余48眼则直接行玻璃体切除术(Ⅱ组)。随访3-12个月(平均7．5个月), 观察患者的视力等术后情况。主要指标视力。结果 94眼术后视力较术前明显提高(P=0．000),其中Ⅰ组治疗有效率优于Ⅱ组 (P=0．029),进一步分析表明在明确眼内炎后7日内即进行玻璃体切除术者无论其术前是否行玻璃体注药术,治疗的有效率差异元统计学意义(P=0．692),但在7天以上者则两组治疗的有效率差异有统计学意义(P=0．008)。结论尽早行玻璃体切除术是治疗外因性眼内炎的有效方法,对于不能尽早施术者,在手术前及时行玻璃体内注射抗生素能明显提高治疗效果。     

抗真菌药伏立康唑在眼科的应用

伏立康唑(VRC)具有良好地血-脑屏障和血-眼屏障穿透功能,无论口服、局部滴眼、角膜基质内注射及玻璃体注射,在房水和玻璃体中均能达到较高的药物质量浓度,房水药物质量浓度超出绝大多数敏感真菌的MIC90,玻璃体腔药物质量浓度也能达到部分真菌的MIC90以上.VRC不仅可用于真菌性角膜炎的治疗,也可用于真菌性眼内炎的预防.局部滴眼目前来说是最安全的治疗方法,眼内注射作为一种有创操作,警惕药物对视网膜的毒性和感染、眼内炎等风险,需严格无菌,熟练操作.在选择治疗方案上,眼科医生应权衡利弊,选择适宜的治疗途径.     

Efficacy of fluconazole and liposome entrapped fluconazole for C. albicans induced experimental mycotic endophthalmitis in rabbit eyes

PURPOSE: To study the efficacy of intravitreally injected plain and liposome encapsulated fluconazole in the doses of 100 and 200 microg in Candidal endophthalmitis in rabbit eyes. METHOD: Endophthalmitis was induced by injecting Candida albicans (1000 CFU/0.1 ml). Seventy two hours after inoculation, plain and liposome encapsulated fluconazole (REVs) were injected. At day 16 sterility was studied using vitreous culture. RESULTS: In the 100 & 200 microg plain fluconazole group, vitreous sterility was seen in 62.5% and 75%, respectively. In the liposome entrapped fluconazole a culture sterility of 25% and 50% for 100 microg and 200 microg, respectively, was seen. CONCLUSION: Plain fluconazole in the dose of 100 and 200 microg was equally effective against Candidal endophthalmitis in rabbits, but a failure of 25-37.5% of the eyes to respond, discourages one from using fluconazole as a sole therapy. Liposome entrapped fluconazole was found to be inferior to plain fluconazole in this model.     

Intravitreal corticosteroids in the treatment of exogenous fungal endophthalmitis.

A rabbit model of exogenous Candida albicans endophthalmitis was used to determine if intravitreal corticosteroids combined with an efficacious antifungal agent enhanced fungal proliferation and ocular destruction, or if the combination can suppress the inflammatory and immunogenic response that causes retinal and uveal destruction. Exogenous Candida albicans endophthalmitis was experimentally induced in 20 rabbit eyes. Eight eyes received intravitreal amphotericin B alone; eight eyes received amphotericin B plus dexamethasone. Four eyes served as controls. By clinical grading on the fourth day after infection, the vitreous of the eyes in the two drug-treated groups was significantly clearer in comparison to that of eyes in the control group. By the seventh day after infection, the eyes treated with amphotericin B plus dexamethasone had significantly clearer vitreous in comparison to the eyes receiving only amphotericin B (P = 0.0017). Quantitative culture results were negative in both treatment groups, and histopathologic examination confirmed the clinical grading. Contrary to current beliefs, there was no evidence that the addition of corticosteroids impaired antifungal activity or enhanced fungal proliferation.     

哌仑西平脂质体在家兔眼内的药代动力学研究

目的研究哌仑西平脂质体结膜囊内应用后在家兔眼部的药代动力学。方法48只家兔随机分为磷酸盐缓冲液组和脂质体组，分别于给药后0．5、1、2、4、6、8、10、12h取材，采用高压液相色谱技术进行测定，3P97软件拟合药代动力学参数，统计学分析采用t检验和单因素方差分析。结果脂质体组各组织中哌仑西平的质量浓度和质量分数较磷酸缓冲液组高，用药2h后各时间点各组织间相比均有显著统计学差异（P〈0．01），它们在各组织中的变化均呈一室开放模型。同一种组织中除脉络膜的消除半衰期外，其余组织各药代动力学参数间（Cmax、t1/2、MRT、AUC）差异有统计学意义（P〈0．05）。巩膜中哌仑西平的质量分数高于脉络膜和视网膜（P〈0．05）。结论哌仑西平脂质体眼部应用有缓释效应，生物利用度高，其很可能是以非角膜途径吸收为主进入眼内的。     

Toward improving therapeutic regimens for Bacillus endophthalmitis

PURPOSE: Bacillus cereus causes the most virulent and refractory form of endophthalmitis. The authors analyzed the effectiveness of early treatment with vancomycin or gatifloxacin, with or without dexamethasone, for experimental B. cereus endophthalmitis. METHODS: Rabbit eyes were injected intravitreally with 100 colony-forming units of B. cereus. At 2, 4, or 6 hours after infection, eyes were injected intravitreally with 0.1 mL gatifloxacin (0.3%), vancomycin (1.0%), either antibiotic plus dexamethasone, dexamethasone alone (1.0%), or PBS. Eyes were analyzed by electroretinography, bacterial quantitation, and antibiotic penetration analysis. Drug toxicity toward Müller cells, retinal pigment epithelium, and cones was also analyzed. RESULTS: Eyes treated at 2 hours with vancomycin or gatifloxacin, with or without dexamethasone, maintained higher ERG amplitudes than the dexamethasone alone and PBS control groups. Eyes treated with antibiotic plus dexamethasone at 6 hours had reduced retinal function compared to antibiotic treatment alone. With the exception of vancomycin with or without dexamethasone at 6 hours, all antibiotic treatments sterilized eyes. Only gatifloxacin reached aqueous concentrations greater than the minimal inhibitory concentration for B. cereus when measured at 8 hours. Neither gatifloxacin nor vancomycin was toxic to retinal cells in vitro. CONCLUSIONS: Early intravitreal injection of vancomycin or gatifloxacin improved the therapeutic outcome of B. cereus endophthalmitis. The addition of dexamethasone to antibiotic treatment did not provide a therapeutic benefit over antibiotics alone and appeared to reduce the antibiotic efficacy of vancomycin 6 hours after infection. In this model, delay in treatment past 6 hours significantly reduced the potential for salvaging useful vision.     

Effects of intravitreal corticosteroid in the treatment of Staphylococcus aureus-induced experimental endophthalmitis

PURPOSE: To investigate whether intravitreal injection of dexamethasone in addition to antibiotics can minimize intraocular tissue injury caused by Staphylococcus aureus endophthalmitis. METHODS: Albino rabbits were infected with an intravitreal injection of 1000 colony-forming units of S. aureus. The rabbits were randomized to receive no treatment (control group; n = 2), intravitreal vancomycin and amikacin (n = 5), or a combination of intravitreal vancomycin, amikacin, and dexamethasone (n = 5) 20 hours following inoculation of bacteria. All rabbits except for the control group also received intravenous imipenem every 8 hours for 4 days. The eyes were evaluated by clinical examination, electroretinogram (ERG), and histologic studies. RESULTS: Eyes treated with intravitreal dexamethasone demonstrated less inflammation on clinical examination compared with eyes that received antibiotics alone. The ERG responses of eyes that received both intravitreal antibiotics and steroid were significantly better at 45 hours, 7 and 14 days following inoculation (P < 0.05) compared to eyes that received antibiotics alone. Histologic studies 14 days following infection demonstrated less tissue destruction for eyes treated with dexamethasone. CONCLUSION: Compared to intravitreal antibiotics alone, intravitreal corticosteroids may improve visual outcome of S. aureus endophthalmitis by reducing inflammation and preserving electrophysiologic retinal function.     

An in vitro study on the compatibility and concentrations of combinations of vancomycin, amikacin, and dexamethasone in human vitreous

PURPOSE: To investigate the precipitation process of a mixture of vancomycin, amikacin, and dexamethasone by equilibrium dialysis and its subsequent effect on the levels of available-free antibiotics and steroid. METHODS: Concentrations of amikacin, vancomycin, and dexamethasone in an equilibrium dialysis chamber were measured during the equilibrium process by high-performance liquid chromatography and fluorescence polarisation immunoassay. Vitreous were used as the medium of dialysis, with the three medications prepared in normal saline (NS) and balanced salt solution plus (BSS Plus) separately. RESULTS: Amikacin showed no measurable loss in NS or BSS Plus, either alone or when mixed with vancomycin or dexamethasone. Vancomycin showed minimal loss in BSS Plus, either alone or when mixed with amikacin or dexamethasone. Dexamethasone showed a median loss of 16 and 15% when incubated alone in NS and BSS Plus, respectively, at 48 h. When mixed with vancomycin or amikacin in BSS Plus, it showed a median loss of 13 and 12%, respectively, at 48 h. There was no statistically significant difference in the loss of dexamethasone under various conditions. In equilibrium dialysis in vitreous, amikacin, vancomycin, and dexamethasone reached equilibrium within 24 h and with no loss up to 192 h. There was no difference observed when the medications were prepared in NS or BSS Plus. CONCLUSIONS: Both amikacin and vancomycin did not show precipitation or decrease in concentration in NS or BSS Plus. Dexamethasone showed relatively small percentage loss. As a result, treatment of endophthalmitis with vancomycin and amikacin combination is preferred.     

16 例白内障术后非感染性眼内炎的临床 分析

目的：探讨白内障术后非感染性眼内炎发生时间、临床表现、危险因素、治疗过程及预后情况。方法： 回顾性研究。收集2020年10月13日至2020年11月19日期间在陆军特色医学中心眼科纳入白内障超 声乳化联合人工晶体植入术患者1004例（1420眼），将发生非感染性炎症与未发生炎症者分为炎症组 与非炎症组，分析术后发生非感染性眼内炎的患者的围手术期所用药物、器械使用及手术操作等环 节，并查找其发病时间、症状、体征、治疗方式以及治疗前后的最佳矫正视力（BCVA）评分等。采 用t检验和重复测量方差分析进行数据处理。结果：发生非感染性眼内炎16例（21眼），其中男5例（7眼）， 女11例（14眼），年龄54~83（68.6±9.5）岁。围手术期所有药品、器械无违规，所有消毒用品消毒指 标均合格，手术操作过程规范，无并发症发生。术中均使用同一品牌型号的疏水性丙烯酸酯人工晶 状体。发病时间为术后（23.3±9.7）d。结膜呈现混合性充血，角膜透明，前房闪辉（+~+++），前房细 胞（++~+++）。部分患者前房内有纤维素性渗出，B超显示玻璃体不同程度的混浊。所有患者前房水 及玻璃体病原微生物检测均为阴性。炎症组与非炎症组术前内皮细胞计数、眼压均为正常，角膜曲 率、眼轴长度差异均无统计学意义。炎症组前房深度明显小于非炎症组，差异有统计学意义（t=-2.55， P=0.010）。结论：本研究中白内障术后非感染性眼内炎高度怀疑与人工晶状体有关，经过积极治疗后， 炎症均得到控制并消退。     

Etiology and diagnosis of bacterial postoperative endophthalmitis.

It is necessary to determine if postoperative endophthalmitis is of infectious or sterile etiology. Intraocular contents should be cultured and were positive in 50% of 58 eyes tested at our institute with suspected postoperative endophthalmitis. The vitreous aspirate is more sensitive than the anterior chamber aspirate in making a diagnosis. The use of a membrane filter to concentrate vitreous samples obtained at vitrectomy increases diagnostic yield. Fifty percent of culture-positive eyes yielded gram-positive organisms. Stained smears were consistent with the cultured organism in half of the cases.     

Retinal vasculitis and posterior pole "hypopyons" as early signs of acute bacterial endophthalmitis

PURPOSE: To report a case of acute postoperative bacterial endophthalmitis presenting with retinal vasculitis and posterior pole "hypopyons." DESIGN: Observational case report. METHODS: Observational case report. RESULTS: In a 73-year-old woman, acute postoperative endophthalmitis presented with retinal vasculitis, diffuse retinal hemorrhages, and several posterior pole "hypopyons" that were collections of yellow-white inflammatory debris. The inflammation was located primarily in the posterior one third of the vitreous, and except for severely impaired visual acuity, the classic signs of acute postoperative endophthalmitis were not present until the next day. An immediate pars plana vitrectomy with intravitreal injection of vancomycin, amikacin, and dexamethasone was performed. Vitreous and aqueous cultures grew coagulase-negative Staphylococcus species. After intravenous and topical therapy for endophthalmitis, the inflammation subsided. Eight weeks after the initial cataract surgery, the best corrected visual acuity of the patient was 20/25. CONCLUSION: Acute postoperative bacterial endophthalmitis may present with atypical clinical signs and inflammation located primarily in the retina and posterior vitreous.