地塞米松-PLGA纳米粒兔眼玻璃体内注射的药物代谢动力学

目的地塞米松(dexamethasone,DM)是眼科临床常用药物,但目前缺乏高效、低毒的给药途径。借助生物降解性多聚体材料聚乳酸-羟乙酸(PLGA)构建DM-PLGA纳米粒,兔眼玻璃体内注射可望在眼后节较长时间维持稳定的有效药物浓度。方法乳化/溶剂蒸发法制备载药量分别为20%和50%的DM-PLGA纳米粒,兔眼玻璃体内注射给药后于第1、7、14和21d分别进行临床观察和组织药物浓度的高效液相色谱分析。结果给药后21d内,角膜和房水中药物浓度均低于检测水平下限(10μg·L-1);血浆药物浓度最高为024mg·L-1;载药量20%和50%的2组中视网膜脉络膜药物浓度分别为011-0.42mg·L-1和0.38-0.88mg·L-1,玻璃体药物浓度分别为0.82-26.52mg·L-1和1.78-85.72mg·L-1。临床观察眼底未见异常。结论载药量50%组的DM-PLGA纳米粒在兔眼玻璃体内可维持药物浓度达3周,提示具有眼内注射应用的潜力。     

贝伐单抗玻璃体腔注射术并发症的临床分析

目的: 观察分析玻璃体腔注射贝伐单抗(bevacizumab)术后并发症的发生率与原因。方法: 随即选择湿性年龄相关性黄斑变性207例207眼,所有病例均行玻璃体腔注射bevacizumab1.5mg/0.06mL。于术后第1d;1,4,12wk除了详细询问主诉,并进行常规视力(最佳矫正视力)、非接触眼压、裂隙灯显微镜、间接眼底镜等检查。结果: 治疗12wk后,视力改善的有效率为90.8%。术后出现眼痛伴异物感7例(3.4%),眼睑皮肤瘙痒1例(0.5%),结膜充血6例(2.9%),球结膜下出血1例(0.5%),术后眼压升高2眼(1.0%)。结论: 玻璃体腔注射bevacizumab的并发症少,安全性高。但需进一步的大样本、随机化、多中心的临床实验,规范该药的临床应用。     

The pharmacokinetics of rituximab following an intravitreal injection

Rituximab is a monoclonal antibody directed against the CD20 B-cell antigen and is approved for the treatment of B-cell lymphoma. We investigated the pharmacokinetics of rituximab following intravitreal administration to assess the feasibility of treating primary intraocular lymphoma. Intravitreal injections of rituximab 0.1 ml (1 mg) were performed in rabbits. Drug concentrations in the aqueous and vitreous humor were measured at intervals from 2 to 17 days after administration. The half-life of the total amount of rituximab in the two compartments was calculated to be 4.7 days. The aqueous and vitreous humor drug levels decayed in parallel maintaining an average ratio of approximately seven. Fitting the data to a two-compartment model yielded a clearance from the aqueous humor of 1.2 microl/min. The clearance was less than the reported rate of aqueous humor outflow indicating that elimination by this route could have been sufficient to account for the disappearance of the drug from the eye. The duration of time over which sustained levels of rituximab were achieved suggest that intravitreal administration warrants further investigation as an approach to treating vitreous and anterior chamber infiltrates in patients with primary intraocular lymphoma.     

Complications in patients after intravitreal injection of bevacizumab

Purpose: To report complications in patients after intravitreal injection of bevacizumab to treat ocular diseases associated with vascular endothelial growth factor. Methods: We retrospectively reviewed the systemic and ocular complications that developed within 2 months of each intravitreal injection of bevacizumab in 707 patients (1300 injections) with intraocular neovascularization or macular oedema. Results: Nine ocular (1.27%) and eight systemic (1.13%) complications occurred in 707 patients. The ocular complications included corneal abrasion (n = 2), chemosis (n = 2), lens injury (n = 1), ocular inflammation (n = 2), retinal pigment epithelial tear (n = 1) and acute vision loss (n = 1). The systemic complications included cerebral infarction (n = 1), elevation of systolic blood pressure (n = 2), facial skin redness (n = 1), itchy diffuse rash (n = 1) and menstrual irregularities (n = 3). Conclusion: Intravitreal injection of bevacizumab may cause systemic or ocular complications. Caution is advised when considering intravitreal injection of this drug.     

Short-term intraocular pressure changes after intravitreal injection of bevacizumab

BACKGROUND: This study examines the changes in short-term intraocular pressure (IOP) in patients receiving intravitreally administered bevacizumab. A prospective series of consecutive patients undergoing injection of intravitreal bevacizumab was investigated. METHODS: All patients received bevacizumab (0.05 cc) injected intravitreally in a standard fashion. IOP was measured at baseline, 2, 5, and 30 minutes after injection by 1 of 2 observers using Goldman applanation tonometry. An intraobserver study was done to assess agreement in IOP measurements. RESULTS: We accrued 104 patients with a mean age of 76 years: 58% were female, and 42% were male. Most patients (85%) were being treated for neovascular age-related macular degeneration. The mean IOP values at baseline, 2, 5, and 30 minutes after injection were 14.0 (95% confidence interval [CI] 13.4-14.7) mm Hg, 36.1 (95% CI 33.5-38.6) mm Hg, 25.7 (95% CI 23.8-27.5) mm Hg, and 15.5 (95% CI 12.4-16.51) mm Hg, respectively. Three patients (2.9%) had an IOP of 25 mm Hg or higher at 30 minutes. IOP normalized within 2 hours without medical therapy in 2 of these patients, and 1 patient required a 1-week course of glaucoma medication. Regression analysis showed a trend towards phakic patients having higher IOP at 30 minutes (odds ratio = 3.2; p = 0.089). INTERPRETATION: Intravitreal injection of bevacizumab is safe with respect to short-term IOP changes, as almost all patients' IOP returned to a safe range (<25 mm Hg) within 30 minutes. Elevated IOP at 30 minutes after injection does occur, rarely, thus clinicians should consider checking IOP after injection as a precaution. Transient extreme IOP elevations occur in a significant percentage of patients, but the consequences of these events are unknown.     

Concentrations of unbound bevacizumab in the aqueous of untreated fellow eyes after a single intravitreal injection in humans

Purpose: To determine the concentration of unbound bevacizumab in untreated fellow eyes after contralateral intravitreal injection of bevacizumab. Methods: A total of 18 eyes received intravitreal injections of 1.5 mg bevacizumab. Nine probes were obtained in the injected eye and nine in the fellow eye. Each group contained three individual eyes. Aqueous humour samples were obtained during uneventful phacoemulsification at three intervals 1–7 days (group a), 8–12 days (group b) or 13–28 days (group c). Results: In untreated fellow eyes, the concentration of unbound bevacizumab was below the detectable limit of the ELISA (5 ng/ml in all samples). The mean concentration of unbound bevacizumab in the injected eye declined from 28.6 μg/ml (group a), 16.5 μg/ml (group b) to 7.4 μg/ml (group c). Conclusions: There are no pharmacological indications for a significant concentration of unbound bevacizumab in the anterior chamber of contralateral eyes in humans.     

姜黄素兔眼玻璃体内注射后眼内毒副作用研究

目的研究不同剂量姜黄素兔眼玻璃体内注射后的眼内毒副作用。方法40只实验兔,随机分为4组，每组10只，一眼为实验眼，玻璃体内分别注射0．05mg／0．1ml、0．1mg，0．1ml、0．2mg，0．1ml姜黄素及0．5‰的DMSO 0．1ml；对侧眼为对照眼，在玻璃体内注射0．1ml生理盐水注射后于第1、第3、第7、第14天进行常规眼部检查和视网膜电图检查：在第3、第7、第14天分别摘取2只眼球做光学和透射电子显微镜检查。结果0．2mg组在注药后第3天和第7天，实验眼暗适应视网膜电图a波振幅分别为（129±9）μV和（131±11）μV，与对照眼的（145＋13）μV和（146＋11）μV相比显著降低（P〈0．01）；实验眼b渡振幅分别为（259±9）μV和（257±7）μV，与对照眼的（283±13）μ V和（276＋8）μV相比显著降低（P〈0．01）。第14天时a波和b波振幅又恢复正常，其余各组各时间段,实验眼a波和b波振幅与对照眼相比差异无统计学意义。各时间段常规眼部检查和视网膜组织学栓查正常。结论 姜黄素玻璃体内注射0．2mg以下剂量是安全可行的。     

Short-term effects of a single intravitreal bevacizumab injection on retinal vessel calibre

Purpose: The aim was to investigate the short‐term effects of a single intravitreal bevacizumab injection on the retinal vessel calibre in patients with neovascular age‐related macular degeneration and in patients with diabetic macular oedema. Methods: Twelve patients with neovascular age‐related macular degeneration and eight patients with diabetic macular oedema were included in the study. All patients received an intravitreal injection of 1.25 mg bevacizumab. Red‐free fundus photographs (35°) were acquired with a fundus camera at baseline and one day, one week and one month after the intravitreal injection. Measurements of retinal vessel diameter were made of the supero‐temporal retinal venule and arteriole using the software available on the IMAGEnet program. Results: Although there appeared to be a trend towards vasoconstriction for the measurements in the diabetic macular oedema group (both for arterioles and venules at day 7) and the age‐related macular degeneration group (for venules at day 1 and for arterioles at day 7), it did not reach statistical significance (p > 0.05). Optical coherence tomography revealed a significant decrease in foveal thickness measurements in both groups at the one month visit compared with baseline. Conclusion: The results suggest that intravitreal injection of bevacizumab might induce retinal vasoconstriction; however, low numbers of subjects might have prevented the difference from reaching statistical significance. Further studies with a larger number of subjects would reveal the effect of intravitreal anti‐vascular endothelial growth factor treatment on retinal vessel diameters more clearly.     

Retinal angiomatous proliferation and intravitreal bevacizumab injection

PURPOSE: To evaluate the short-term efficacy and safety of intravitreal bevacizumab injection (IVBI) in patients with retinal angiomatous proliferation (RAP). METHODS: Seven eyes of 5 patients with RAP were included in this study. All of the eyes evidenced stage 2 RAP lesions, except for one eye with a stage 3 lesion. IVBI (1.25 mg/0.05 cc) were conducted at 4 or 6-week intervals. Complete ocular examinations, angiographic results and optical coherence tomographic findings before and after the IVBI were analyzed at baseline and upon the follow-up visits. RESULTS: Seven eyes were studied in 5 patients who had undergone IVBI. Partial (3 eyes) or complete (4 eyes) regression of RAP was noted after IVBI in all of the studied eyes. Visual acuity improved in 5 of the eyes, and was stable in 2 of the eyes. One eye evidenced severe intraocular inflammation after IVBI and a subsequent development of new RAP, which was controlled with vitrectomy and repeat IVBI. CONCLUSIONS: This treatment was effective over 6 months, stabilizing or improving visual acuity and reducing angiographic leakage. These short-term results suggest that IVBI may constitute a promising therapeutic option, particularly in the early stages of RAP.     

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.     

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.     

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。     

Testing toxicity of multiple intravitreal injections of bevacizumab in rabbit eyes

Objective: To evaluate the potential toxicity of repeated intravitreal injections of bevacizumab in rabbit eyes.Design: Randomized, placebo-controlled experimental animal study.Participants: Fourteen chinchilla rabbits; 12 assigned to the experimental group and 2 assigned to the normal control group.Methods: Three sequential, biweekly, intravitreal injections of bevacizumab in doses of 2.5 mg/0.1 mL or 5.0 mg/0.2 mL were performed on each rabbit. Evaluations included intraocular pressure (IOP), aqueous flare, B-scan ultrasound, fundus photography, ultrasound biomicroscopy, electroretinography (ERG), and visually evoked potentials (VEPs) performed at baseline and during the follow-up period. The eyes were enucleated at 1 week and 4 weeks after the last intravitreal injection, and underwent light and electron microscopic evaluations, as well as testing for apoptotic activity.Results: After intravitreal injections, no changes were found by regular clinical observation and IOP tests. There was no significant difference in the anterior chamber inflammatory activity evaluated by the laserflare meter. No evidence of retinal toxicity was seen after intravitreal bevacizumab at doses of 2.5 and 5.0 mg by either ERG or flash VEPs. Electron microscopy did show the presence of inflammatory cells and some ultrastructural changes in the photo-receptor cells in the 5.0 mg experimental group 1 week after the third injection. Mild to moderate apoptosis of photoreceptors was detected in the 5.0 mg group at the same time.Conclusions: The biweekly, multiple intravitreal injections of bevacizumab did not result in evidence of toxicity in regular clinical and functional observations at both 2.5 mg and 5.0 mg doses. The 5.0 mg dose may induce transient inflammation, ultrastructural abnormalities, and apoptosis.     

Lack of positive effect of intravitreal bevacizumab in central serous chorioretinopathy: meta-analysis and review

Purpose

To review and evaluate the effects of intravitreal bevacizumab injection (IVB) in centralserous chorioretinopathy (CSC) by meta-analysis.

Patients and methods

Clinical controlled studies that evaluated the effect of IVB in CSC were identified through systematic searches of Embase, PubMed, and the Cochrane Central Register of Controlled Trials. Data on the best-corrected visual acuity (BCVA) in logMAR and central macular thickness (CMT) in μm at baseline and 6 months after IVB were extracted and compared with those treated by simple observation.

Results

Four clinical controlled studies were included in the meta-analysis. The IVB injection group achieved better BCVA at a follow-up of 6 months. However, the analysis showed that there were no significant differences of BCVA at 6 months after injection between IVB group and the observation group (−0.02 logMAR, 95% CI −0.14 to 0.11, P=0.80). The analysis of the reduction in CMT revealed that the difference between groups was not statistically significant (−8.37 μm, 95% CI −97.26 to 80.52, P=0.85). No report assessed severe complications or side effects of IVB in patients with CSC.

Conclusions

Meta-analysis failed to verify the positive effect of IVB in CSC based on the epidemiological literature published to date.     

玻璃体腔注射抗VEGF治疗的回顾性分析

目的：回顾分析佛山市第二人民医院眼科中心2013/2015年行玻璃体腔注射抗VEGF在眼底新生血管性疾病中的应用情况。
　　方法：回顾性分析2013-01/2015-12期间在佛山市第二人民医院眼科中心的住院患者,以手术方式为“玻璃体腔内注药术”为检索词查阅病历管理系统,排除玻璃体腔注射曲安奈德及抗生素药物的患者,就其相关疾病进行统计分析。同时查询相关疾病同年收住院患者资料并进行对比。
　　结果：3 a间共行239眼注射,男女比例接近,青年、中年及老年组间无统计学差异,3a间注射人数逐年增加。行抗VEGF( vascular endothelial growth factor )注射的相关疾病主要为脉络膜新生血管性疾病、视网膜静脉阻塞、糖尿病性视网膜病变及息肉状脉络膜血管病变,同一年度四类疾病及同种疾病不同年度行抗 VEGF 注射比率(注射/总数)有显著性统计学差异,其中脉络膜新生血管性疾病患者3a中接受注射程度最高,息肉状脉络膜血管病变则增长最快。
　　结论：抗VEGF玻璃体腔注射作为眼底新生血管性疾病新的治疗方式,正日益为患者接受。     

兔眼玻璃体腔内注射纤维蛋白溶酶诱导产生玻璃体后脱离

目的 观察兔眼玻璃体腔内注射1U纤维蛋白溶酶（后诱导产生玻璃体后脱离（PVD）的情况。方法 以16只新西兰兔作为实验动物，所有右眼内注入1U纤溶酶，按设定的4个观察时间点随机分为4组。通过临床肉眼观察，视网膜电图（ERG）和组织病理学检查，考察药物注入后诱导形成PVD的情况以及药物应用的安全性。结果 玻璃体腔内注入1U纤溶酶后15min-3d，药物对视网膜结构和功能没有任何不良影响；第1d组开始有PVD发生。第3d组效果更佳。结论 1U纤溶酶可以用作玻璃体切割手术的辅助用药。     

阿瓦斯汀玻璃体腔内注射治疗黄斑水肿的临床观察

目的探讨阿瓦斯汀（Avastin）玻璃体腔内注射治疗黄斑水肿的临床效果。方法自2008年1月至2009年9月在我科就诊的手术后黄斑水肿和其它原因的黄斑水肿196例226眼,随机分为两组：阿瓦斯汀玻璃体腔内注射组100例116眼,采用阿瓦斯汀玻璃体腔内注射治疗;激光光凝治疗组96例110眼,采用激光光凝治疗。观察两组临床疗效。结果阿瓦斯汀玻璃体腔内注射组总有效率92.24%,激光光凝治疗组总有效率71.81%,两组总有效率比较差异有统计学意义（P〈0.05）。结论应用阿瓦斯汀玻璃体腔内注射治疗黄斑水肿,具有临床疗效确切、应用安全、操作简单、痛苦少及并发症较少等优点,值得临床应用。     

Rapid resolution of severe disc new vessels in proliferative diabetic retinopathy following a single intravitreal injection of bevacizumab (Avastin)

A 70-year-old man with asymptomatic proliferative diabetic retinopathy received a single intravitreal injection of bevacizumab (Avastin). One month following treatment there was complete resolution of new vessels.