姜黄素防治兔眼增生性玻璃体视网膜病变的实验研究

背景先前的系列研究表明,姜黄素可以诱导体外培养的兔视网膜色素上皮（RPE）细胞凋亡,抑制其RPE细胞的增生,且在玻璃体内应用后不良反应较小,具有防治增生性玻璃体视网膜病变（PVR）的潜在价值。目的探讨姜黄素玻璃体内注射对RPE细胞诱导的兔眼PVR模型的防治效果。方法新西兰白兔20只40只眼,所有兔眼玻璃体注射前先抽取0．2ml玻璃体液,然后在兔眼玻璃体内注射0．1ml（2×10^6）同种RPE细胞,每只兔随机选取1只眼立即注入1mg／L的姜黄素0．1ml作为姜黄素组（20只眼）,对侧眼注入等量的含质量分数0．5‰DMSO的生理盐水作为对照组（20只眼）。注药后1、3、7、14、21、28d裂隙灯显微镜下观察角膜、房水、晶状体的透明度及眼前节炎症反应情况;使用间接检眼镜、眼底彩色照相和B型超声检查玻璃体视网膜情况。以视网膜脱离发生眼数作为检测指标,评价姜黄素对PVR的防治效果。结果玻璃体注药后1d、3d所有兔眼发生眼前节炎症反应,玻璃体轻中度混浊,但未见增生条带及视网膜脱离。玻璃体注药后7d,所有兔眼前节炎症反应基本消退,对照组14只眼（75％）玻璃体出现增生条带,姜黄素组2只眼（10％）玻璃体内出现增生条带,差异有统计学意义（P〈0．01）,但2组均未见视网膜脱离。注药后14d,对照组11只眼（55％）出现视网膜脱离,姜黄素组2只眼（10％）出现视网膜脱离,差异有统计学意义（P〈0．01）;注药后21d,对照组16只眼（80％）出现视网膜脱离,姜黄素组3只眼（15％）出现视网膜脱离;注药后28d,对照组19只眼（95％）出现视网膜脱离,姜黄素组3只眼（15％）出现视网膜脱离,差异有统计学意义（P〈0．01）。结论姜黄素玻璃体腔内注射可以有效预防RPE细胞诱导的兔眼实验性PVR的发生发展。     

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。     

谷氨酸兔玻璃体内注射对视网膜电图的影响

目的 探讨不同质量浓度谷氨酸对实验兔视网膜电网（ERG）的影响。方法 通过兔玻璃体内注入不同质量浓度的谷氨酸，观察注射前后不同时间ERG变化。结果 F-ERGb波，OPs波，在兔玻璃体内注入谷氨酸100μg/20μl时，波幅显著下降，随着时间的推移渐恢复，但注入300μg/20μl和600μg/20μl波幅显著下降，7天时仍未恢复，大剂量组与小剂量组相比ERG波波幅有显著差别；注入600μg/20μl谷氨酸同时注射40μg/20μl谷氨酸NMDA受体拮抗剂MK-801，ERG无显著变化。结论 兔眼玻璃体注入的谷氨酸大于或/和等于100μg时对视网膜的功能产生影响；大于或/和等于300μg时对视网膜有严重的毒性作用。且具有剂量依赖性，MK-801对其具有重要的保护作用。     

玻璃体内注射雷珠单抗治疗早产儿视网膜病变

目的　观察玻璃体内注射雷珠单抗治疗早产儿视网膜病变（ｒｅｔｉｎｏｐａｔｈｙｏｆｐｒｅｍａ-ｔｕｒｉｔｙ,ＲＯＰ）的疗效及其安全性。方法　回顾分析了２０１２年１１月至２０１４年５月于北京同仁医院治疗的１７例（３１眼）ＲＯＰ患儿,在４８ｈ内行玻璃体内注射雷珠单抗,对注射后无反应者,重复玻璃体内注射雷珠单抗或联合激光光凝治疗,术后１ｄ、１个月内每周随访观察复诊。结果　所有治疗眼中,单纯行玻璃体内注射雷珠单抗２７眼,玻璃体内注射雷珠单抗联合激光治疗４眼。２８眼进行了一次治疗,３眼经过了二次注射治疗;４眼进行补充视网膜激光治疗。所有的ＲＯＰ治疗均有效,随访期内未见有复发病例。结论　玻璃体内注射雷珠单抗对ＲＯＰ的治疗效果可靠,尤其对于病情严重、全身情况差不能耐受全身麻醉的患儿,其优势明显。     

玻璃体积血对兔眼视网膜影响的研究

目的　观察兔眼玻璃体积血后不同时间视网膜电图（electroretinogram,ERG）及超微结构的变化,为玻璃体积血治疗及预后评估提供实验依据。方法　新西兰大白兔32只,右眼均为实验眼,自体全血0.2 mL玻璃体内注射构建玻璃体积血模型,左眼为空白对照眼。随机分为4组,分别于造模后3 d、7 d、14 d及30 d选取一组常规检查后记录ERG的变化,随后处死动物立即摘取眼球制备标本观察超微结构。结果　实验性玻璃体积血3 d后常规ERG波形消失,造模后7 d逐渐出现。强闪光源刺激下,造模后3 d实验眼ERG的b波振幅与a波振幅与对照眼相比均明显降低（均为P＜0.01）。a波振幅在造模后30 d明显恢复,与对照眼无明显差异（P＞0.05）,较造模后14 d差异有统计学意义（P＜0.05）;b波振幅在造模后7 d时开始回升,与对照眼无明显差异（P＞0.05）,较造模后3 d差异有统计学意义（P＜0.05）,造模后14 d及30 d接近正常。扫描电镜显示实验眼造模后3 d无玻璃体后脱离（posterior vitreous detachment,PVD）发生,造模后7 d部分性PVD占1/8,完全性PVD占1/8,造模后14 d部分性PVD占2/8,完全性PVD占5/8,造模后30 d部分性PVD占1/8,完全性PVD占7/8;对照眼各阶段未见PVD发生。结论　玻璃体积血后约1周可轻度可逆地影响视网膜功能并加速导致PVD形成,为实验及临床判断玻璃体积血后视网膜功能变化和临床玻璃体手术治疗的时间窗的选择提供了参考。     

玻璃体内注射曲安奈德治疗糖尿病视网膜病变及其并发症

玻璃体内注射曲安奈德被越来越多地应用于糖尿病视网膜病变中,如糖尿病黄斑水肿、增生性糖尿病性视网膜病变、由增生性糖尿病性视网膜病变引起的新生血管性青光眼和糖尿病性视网膜病变手术后持续性低眼压的并发症等。同时随着应用的日益广泛,其产生的并发症也越来越不容忽视,其并发症主要有眼压升高、眼内感染等。我们总结介绍了玻璃体内注射曲安奈德在糖尿病视网膜病变方面的运用,并就其产生的常见并发症作一扼要综述。     

硅油在现代玻璃体视网膜手术中的应用

目的 通过回顾性分析及比较了解硅油在现代玻璃体手术中的应用及硅油对增殖性玻璃体视网膜病变（proliferative vitreoretinopathy,PVR)及增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR) 中的疗效。方法 分析1993年1月－1997年12月在国立名古屋医院接受玻璃体切割手术治疗的患者,选出应用硅油的112例;并选择其中合适的80眼进行进一步分析。结果 与过去相比硅油在PVR和PDR中的指征有不同程度的变化。在28．2个月的随访后,PVR组取得了73．5％的视网膜复位率,同时大部分患者在术后能获得视力改善或保持原有的视力;PDR组则仅维持术前视力,且在长期随访之后,视力有明显下降;另一方面硅油在虹膜新生血管的眼中未能取得预期的疗效。术后并发症方面,PDR组仅在视网膜前出血方面多于PVR组。结论 硅油在复杂性PVR及PDR的治疗中发挥着重要的作用,硅油的指征在近年来已有所变化;同时在某些方面硅油的疗效有待进一步研究;尽管采取了多种防治手段,硅油仍可产生一定的并发症。     

增殖性玻璃体视网膜病变的玻璃体手术治疗

目的 评估玻璃体手术治疗增殖性玻璃体视网膜病变的疗效。方法 Ｃ２级以上ＰＶＲ合并视网膜脱离２１眼,特发性ＰＶＲ１４眼,外伤性ＰＶＲ７组,Ｃ级９眼,Ｄ级１２眼,均作常规玻璃体切除术联合环扎、膜剥离、视网膜切开、气体或硅油填充等附加术式。结果随访２～９个月,视网膜复位１５眼（７８．９％）,视力提高２０眼（９５．２％）。４眼手术失败,均系ＰＶＲ再次复发所致。结论 现代玻璃体手术是治疗严重ＰＶＲ的理想术     

纤维蛋白胶玻璃体内注射对兔视网膜的毒性作用观察

目的观察纤维蛋白胶玻璃体内注射对兔视网膜的毒性。设计实验性研究。研究对象28只青紫蓝兔。方法将28只青紫蓝兔随机分为4组,每组7只。4组动物中的3组右眼玻璃体内分别注入剂量为0．1ml、0．2ml、0．4ml的纤维蛋白胶,盔白对照组右眼玻璃体内注入0．2ml生理盐水。注射后1天、7天、14天及28天行裂隙灯、间接检眼镜、视网膜电流图（ERG）检查,观察暗适应最大反应b波波幅,最后一次检查后取眼球行病理切片光镜检查,观察视网膜各层细胞形态、排列。主要指标实验动物眼术后KP、闪光,视网膜皱褶的发生情况,ERG暗适应最大反应b波波幅,视网膜病理切片光镜下各层细胞的形态、排列情况。结果实验组眼术后未观察到明显的KP、闪光等炎性反应证据,未观察到视网膜皱褶形成、玻璃体视网膜牵拉等增生性玻璃体视网膜病变（PVR）发生的证据,ERGb波幅较对照组变化无显著性差异,病理切片光镜下视网膜各层细胞形态、排列未见异常。结论玻璃体内注射≤0．4ml的纤维蛋白胶是安全的。     

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.     

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.     

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。     

康柏西普玻璃体腔注射后患眼短期眼压升高的影响因素分析

目的：探讨分析玻璃体腔注射康柏西普后短期眼压(IOP)升高的影响因素。

方法：临床前瞻性观察研究。共纳入玻璃体腔注射康柏西普的视网膜病变患者269例269眼,所有患眼均行康柏西普玻璃体腔注射治疗。其中,男143例,女126例; 年龄相关性黄斑变性(ARMD)患者201例,其他类型视网膜变性患者68例。平均年龄62.86±11.74岁,采用非接触气动式眼压计,分别在注射前,注射后10、30min,2和4h对患者进行IOP测量。根据注射后10min IOP升高情况来进行分组,IOP升高10 mmHg及以上定义为IOP升高组,IOP升高小于10 mmHg定义为IOP稳定组。采用多因素Logistic回归分析分析两组之间的差异。

结果：患者在注射后10、30min,2和4h的平均IOP分别为24.1、20.2、19.5、16.9 mmHg,注射后各个时间点的IOP较注射前平均升高6.7、3.1、1.7、0.5 mmHg。其中,IOP高组56例,IOP稳定组213例。两组患者年龄、最佳矫正视力(BCVA)、性别、眼别、疾病类型比较均无统计学差异(均P>0.05); 注药次数(Z=-4.389,P=0.012)、注射前IOP及注射后各时间点的IOP(t=-5.343,-10.467,-8.933,-6.124,-4.635,均P<0.01)比较差异均有统计学差异。多变量Logistic回归分析显示,基础IOP与注射后10min IOP升高呈正相关(B=-0.913,OR=0.521,95%CI：0.211～0.694,P=0.011)。

结论：基线IOP水平越高,注射后IOP升高的风险越高。基线IOP是影响玻璃体腔注射康柏西普后患眼短期IOP升高的主要相关因素,而注射次数可能是另一个风险因素。     

Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes

Background: Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short. To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate the retinal toxicity of liposome-incorporated and free OFLX. Materials and methods: OFLX was incorporated into multilamellar large vesicles. 0,1 ml of this suspension (= 180.2 μg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free OFLX in doses of 100 μg, 500 μg and 1,000 μg was injected into the midvitreous of a second group of rabbit eyes (n = 18). The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light- and transmission electron microscopy. Results: The ERG as well as the histologic studies did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant reduction of the ERG was observed after 500 μg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes 1 day after 1,000 μg free OFLX. Three days after injection of 1,000 μg OFLX the retina showed focal destruction in 1 out of 6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation. Conclusion: This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 μg after intravitreal injection. Injection of higher doses resulted in ERG changes and marked retinal damage. This revised version was published online in July 2006 with corrections to the Cover Date.     

玻璃体腔内注射术中行前房穿刺对术后早期眼压的影响

目的:观察玻璃体腔内注射康柏西普术中行前房穿刺对术后早期眼压的影响.方法:将接受玻璃体腔注射康柏西普治疗的30例患者随机分为两组:前房穿刺组(A组)和未行前房穿刺组(B组),A组在玻璃体腔内注射康柏西普同时行前房穿刺,B组仅玻璃体腔内注射康柏西普.应用AccuPen手持式回弹眼压计于治疗前及治疗后2、30、60min,1d,1wk测量眼压,并进行比较.结果:与术前眼压比较,A组术后各时间点眼压变化无统计学差异(P>0.05);B组术后2min眼压骤升至42.4±9.3mmHg,与A组同时间点眼压比较,差异有统计学意义(P<0.05);30min时降至17.4±5.0mmHg,与A组同时间点眼压比较,差异无统计学意义(P>0.05).结论:玻璃体腔注射康柏西普术中行前房穿刺能够有效控制注射后的早期眼压升高.     

玻璃体腔内注射曲安奈德后早期眼压变化和前房穿刺对眼压的影响

目的观察玻璃体腔内注射曲安奈德（TA）后眼压的早期变化以及前房穿刺对眼压的影响。方法将接受玻璃体腔内注射TA治疗的20例20眼患者随机分为前房穿刺组（A组）和未进行前房穿刺组（B组）,各10例10眼。A组在玻璃体腔内注射TA后前房穿刺并抽取0.05 mL房水,B组仅玻璃体腔内注射TA。应用Goldmann眼压计于玻璃体腔内注射前及注射后2、15、30 min,1 h,1 d,1周测量眼压,对2组注射前后眼压的变化进行对比研究。结果 A组注射前平均眼压为（13.70±2.52）mmHg,注射后2 min时为（8.20±1.33）mmHg,15 min时为（11.32±1.52）mmHg,A组注射后2 min时的眼压明显低于组内其他时间点,差异均有统计学意义（P〈0.01）。B组注射前平均眼压为（15.32±1.73）mmHg,注射后2 min时为（39.23±9.31）mmHg,15 min时为（16.24±3.52）mmHg,B组TA注射后2 min眼压明显高于注射前,差异有统计学意义（P〈0.01）,注射后15 min恢复到正常眼压水平（16.24±3.52）mmHg。A组在注射后2 min的眼压明显低于B组同时间点的眼压,差异有统计学意义（P〈0.01）。A组注射后早期可见一过性前房闪辉,B组未见眼部不良反应。结论玻璃体腔内注射TA后早期可引起一过性眼压升高,可选择性进行前房穿刺。前房穿刺和玻璃体腔内TA注射是安全的。     

增生型糖尿病性视网膜病变术前玻璃体内注射曲安奈德的价值

目的　探讨术前玻璃体内注射曲安奈德（ｔｒｉａｍｃｉｎｏｌｏｎｅａｃｅｔｏｎｉｄｅ,ＴＡ）对于增生型糖尿病性视网膜病变（ｐｒｏｌｉｆｅｒａｔｉｖｅｄｉ-ａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＰＤＲ）行玻璃体视网膜手术效果的影响。方法　选择我院２０１４年３月至２０１５年６月收治的ＰＤＲ患者（Ⅴ期或Ⅵ期）６０例（６０眼）。随机分为治疗组（术前１周行玻璃体内注射ＴＡ）和对照组（直接行玻璃体切割术）,每组３０例。比较两组患者术中出血情况、医源性视网膜裂孔发生率、眼内填充物的使用、平均手术时间及术后视力。结果　治疗组术中发生中、重度出血率为１６．７％,显著低于对照组的３６．７％,差异有统计学意义（Ｐ＜０．０５）;治疗组术中医源性视网膜裂孔发生率为１０．０％,显著低于对照组的３３．３％,差异有统计学意义（Ｐ＜０．０５）;治疗组硅油填充率为４０．０％,对照组为６０．０％,差异无统计学意义（Ｐ＞０．０５）;治疗组手术时间为（４０．２３±１３．９０）ｍｉｎ,明显短于对照组的（５５．８２±１４．４３）ｍｉｎ,差异有统计学意义（Ｐ＜０．０５）;治疗组术后视力为０．３１６±０．１０１,优于对照组的０．２０２±０．１３２,差异有统计学意义（Ｐ＜０．０５）。结论　ＰＤＲ患者在玻璃体切割术前１周行玻璃体内注射ＴＡ,可降低手术难度,减少术中并发症,进而缩短手术时间,有助于术后视力改善。