那素达滴眼液在LASIK术中应用的临床对比观察

目的对比观察准分子激光原位角膜磨镶术（LASIK）前应用那素达滴眼液及不同点眼次数对结膜下出血的影响。方法研究分为临床对照研究和自身对照研究。临床对照研究：观察组在术前15min滴那素达滴眼液1次,对照组在术前15min开始滴那素达滴眼液,间隔5min滴眼1次,共3次。自身对照研究：在术前15min给同一患者左眼滴那素达滴眼液1次,右眼滴那素达滴眼液,间隔5min滴眼1次,共3次,下1例右眼滴1次,左眼滴3次,依次类推准备术眼。两组均按常规进行LASIK术前准备及手术。结果临床对照组和自身对照组中,观察组与对照组术后3个月裸眼视力比较差异无统计学意义。临床对照组中,观察组有4眼发生结膜下出血,占3．67％;对照组有5眼发生结膜下出血,占4．59％,两组比较差异均无统计学意义。自身对照组中,观察组有3眼发生结膜下出血,占3．12％：对照组有4眼发生结膜下出血,占4．16％,两组比较差异均无统计学意义。结论在LASIK术前点用那素达滴眼液,能有效地降低LASIK术后结膜下出血的发病率,并且点眼1次或3次对结膜下出血的发病率无影响。     

冠状动脉直接支架术与常规支架术的对比研究

目的:与球囊预扩张后置入支架的常规支架术相比较,分析冠状动脉直接支架术的可行性、安全性及其临床疗效.方法:选择389例行冠脉介入治疗并置入金属裸支架的患者,分为A、B两组进行比较分析,其中A组187例患者的214处病变施行了直接支架术.B组202例患者的276处病变施行了预扩张置入支架术.两组患者的临床及冠脉造影特征相似,将两组的介入治疗结果相比较.结果:A组187例患者中181例成功施行直接支架术,技术成功率96.8%:6例患者换为常规支架术而顺利置入支架,介入手术成功率100%.两组患者支架置入成功率无差异,A组手术操作时间较短、球囊导管用量较少(P<0.01)、X线暴光时间较短、造影剂用量较少、手术费用较低(P<0.05).A、B两组分别有3例(1.6%)和17例(8.4%)术中发生血管撕裂夹层(P<0.05).术后12～36个月随访显示,A组有10例患者(5.3%)心绞痛复发,9例患者经心电图活动平板试验证实有心肌缺血复发,这19例复发患者经CAG复查示14例(7.5%)为支架内再狭窄:B组有26例患者(12.9%)心绞痛复发,6例患者活动平板试验心肌缺血复发,复查CAG显示其中20例(9.9%)为支架内再狭窄.临床随访期内A组心绞痛复发率低于B组(P<0.05).结论:直接支架术是一种安全、有效、易行的冠脉介入治疗技术,其术中血管并发征及术后心绞痛发生率较低.     

A method for enhancing the ocular penetration of eye drops using nanoparticles of hydrolyzable dye

This report describes a method for enhancing the ocular penetration of eye drops using nanoparticles of hydrolyzable dye, which is similar to a prodrug approach. The entry of eye drops into the ocular globe is restricted predominantly by corneal barrier functions. The barrier functions are epithelial tight junctions as well as a physicochemical property consisting of the opposite characteristics of a lipophilic epithelium and a hydrophilic stroma. We found that using a formulation of nanoparticles of hydrolyzable dye (with particles of 200 nm in diameter on average) attained a greater than tenfold higher (about 50-fold) ocular penetration than that of micron-sized particles. The nanoparticles were prepared by a carrier-free technique; i.e., the reprecipitation method. Confocal laser fluorescence microscopy showed that dyes originating from the nanoparticles surmounted the corneal epithelium barrier, which has tight junctions, and achieved deeper penetration into the cornea. The high penetration rate of the dyes into the cornea was attributed to the size of particles (i.e., nanoparticles) and a transformation of dye polarity from lipophilic to hydrophilic in in vivo hydrolysis reactions. We concluded that utilizing in vivo hydrolysis reactions to alter the physicochemical nature of nanoparticles consisting of hydrolyzable compounds was an effective approach for enhancing the ocular penetration of eye drops.     

含与不含抗胸腺细胞球蛋白的两种预处理方案早期毒性的比较

目的 比较采用改良白消安/环磷酰胺(Bu/Cy)方案及改良Bu/Cy+抗胸腺细胞球蛋白(ATG)方案进行预处理的异基因造血干细胞移植(HSCT)患者在预处理期间及移植后早期发生的相关毒性.方法 100例血液系统恶性肿瘤患者中,应用改良Bu/Cy方案者(A组)42例,应用改良Bu/Cy+ATG方案者(B组)58例,主要观察预处理期间及移植后早期出现的非感染性发热、腹泻、肝毒性、黏膜炎及血液系统毒性.结果 A、B两组发热发生率分别为4.8%和81.0%,转氨酶升高发生率分别为59.5%和65.5%,胆红素升高发生率分别为16.7%和48.3%,腹泻发生率分别为59.5%和79.3%,黏膜炎发生率分别为45.2%和37.9%.白细胞进入零期的中位时间分别为+3 d和-3 d;-10 d内需输注红细胞及血小板的比例分别为11.9%和32.8%,16.7%和82.8%.结论 含ATG的预处理方案组发热,腹泻,肝损害,白细胞、红细胞和血小板降低的发生率明显高于不含ATG的预处理方案组,这种改变很可能与ATG相关.     

Blood derived eye drops for the treatment of cornea and ocular surface diseases

The use of blood derived eye drops for the treatment of ocular surface disorders has become increasingly popular in recent years. The mechanism of action is the stimulation of cellular proliferation and migration by supplying an active mixture of growth factors and cytokines at the ocular surface, thus mimicking the function of the lacking natural tears. Blood derived eye drops have been used in the last decades for the treatment of a variety of ocular surface diseases, including mainly dry eye disease, persistent corneal epithelial defect, corneal ulcer, ocular surface burn, recurrent corneal erosion and limbal stem-cell deficiency. Among overall blood derived eye drops, both autologous (from the patients themselves) and homologous (from donors) products exist, with different advantages and disadvantages. Autologous serum, obtained from the patient's own peripheral blood, is the first introduced and most commonly used product. Despite several randomized clinical trials showed its safety and efficacy, a recent Cochraine meta-analysis failed to show significant results due to low evidence. Homologous sources including allogeneic serum obtained from healthy donors, and umbilical cord blood serum collected at the time of delivery, are efficient alternatives, especially when autologous serum therapy is contraindicated or not appropriate. Platelet-derived eye drops are prepared and used in various but poor standardized preparations, namely platelet-rich plasma, plasma rich in growth factors, and platelet lysate. Future perspectives of blood-derived products include the introduction of tailored eye drops, screened for the proper content of growth factors and cytokines according to each patient and ocular surface disease.     

Effects of travoprost eye drops on intraocular pressure and pulsatile ocular blood flow: a 180-day, randomized, double-masked comparison with latanoprost eye drops in patients with open-angle glaucoma

Background: Because of the increasing realization of the importance of optic nerve head perfusion in the pathogenesis of glaucoma, the influence of new antiglaucomatous drugs on ocular hemodynamic properties should be investigated.Objective: The aim of this study was to compare the effects of 2 prostaglandin analogues, travoprost eye drops and latanoprost eye drops, on intraocular pressure (IOP) and pulsatile ocular blood flow (pOBF) in patients with primary open-angle glaucoma (POAG).Methods: Previously untreated patients aged 40 to 60 years with POAG and normal brachial blood pressure (BBP), heart rate, body mass index, and hemorheologic findings were eligible for this randomized, double-masked study. Two drops of travoprost (group T) or latanoprost (group L) were self-administered in both eyes at 9:00 pm. In all patients, IOP, pOBF, BBP, and heart rate were measured at baseline and on days 15, 30, 60, 90, and 180 of treatment.Results: Twenty-five consecutive patients with POAG were enrolled in this study conducted at the Glaucoma Research Center of the Department of Ophthalmology, Bari University, Policlinico di Bari (Bari, Italy). Of these, 7 were withdrawn because they did not return for the second appointment, leaving 18 patients (11 men, 7 women; mean [SD] age, 51.9 [5.5] years) to complete the study. In both groups, mean IOP values were significantly reduced at all time points compared with baseline (all P<0.01). Mean pOBF values increased ∼50% from baseline following treatment with either travoprost or latanoprost by day 15, were maintained at that level for 60 days, and then gradually decreased (group T: P = NS, NS, <0.01, <0.05, and <0.05 at days 15, 30, 60, 90, and 180, respectively, vs baseline; group L: P<0.01 at all time points vs baseline). All other parameters remained constant throughout the study. An early inverse correlation between IOP and pOBF was noted in group T but not in group L. No significant differences were found between groups in IOP or pOBF at any time point.Conclusions: In this study population, pOBF was increased with travoprost and latanoprost in the short term, but this effect was kept constant only with travoprost. IOP was reduced with both drugs after short-term therapy, and this reduction was maintained in both groups. Travoprost may represent another option for the medical treatment of POAG.     

普拉洛芬联合rhEGF滴眼液治疗白内障术后干眼症的效果

目的探讨普拉洛芬联合重组人表皮生长因子(rhEGF)滴眼液治疗白内障术后干眼症的临床效果。方法将白内障术后发生干眼症的患者94例随机分为普拉洛芬组和联合治疗组,每组47例。普拉洛芬组采用普拉洛芬滴眼液治疗,联合治疗组采用普拉洛芬滴眼液联合rhEGF滴眼液治疗。比较两组患者临床疗效、干眼症状评分、泪膜破裂时间(BUT)、泪液分泌长度、角膜荧光素染色(FL)评分和泪液炎性因子水平。结果普拉洛芬组治疗总有效率为83.12%,显著低于联合治疗组的97.47%(P<0.05)。治疗后,两组干眼症状评分均降低,且联合治疗组显著低于普拉洛芬组(P<0.05)。治疗后,联合治疗组BUT、泪液分泌长度显著长于普拉洛芬组,FL评分显著低于普拉洛芬组(P<0.05)。治疗后,两组泪液IL-1β、IL-6、TNF-α水平均较治疗前显著下降,且联合治疗组低于普拉洛芬组(P<0.05)。结论普拉洛芬滴眼液联合rhEGF滴眼液可促进白内障术后干眼症泪膜修复、减轻炎症反应,改善干眼症状。     

角膜缘干细胞移植术后应用玻璃酸钠滴眼液对翼状胬肉复发率及眼表症状的影响

目的探讨角膜缘干细胞移植术(LCAT)后应用玻璃酸钠滴眼液预防翼状胬肉的效果及对眼表症状的影响。方法选择2018年11月至2019年11月住院治疗的66例翼状胬肉患者,以随机抽签法将其分为观察组和对照组,每组33例。所有患者均行翼状胬肉切除术配合LCAT,对照组术后予以抗生素联合糖皮质激素滴眼,观察组在对照组基础上加用玻璃酸钠滴眼液。比较两组患者的治疗效果。结果观察组的治疗总有效率高于对照组,复发率低于对照组(P<0.05);观察组术后2、6、8 d的眼表症状评分均低于对照组(P<0.05);观察组术后2、3 d的角膜上皮愈合率高于对照组(P<0.05);术后3个月,观察组的SⅠt、BUT优于对照组,FL评分低于对照组(P<0.05)。结论LCAT术后应用玻璃酸钠滴眼液可显著改善翼状胬肉患者的眼表症状、眼表功能,促进角膜上皮愈合,预防复发。     

Chronic benzodiazepine administration. VI. A partial agonist produces behavioral effects without tolerance or receptor alterations

Chronic benzodiazepine administration has been reported to lead to behavioral tolerance and, in some cases, downregulation of gamma-aminobutyric acid A (GABAA)-receptor binding and function. So-called "partial agonist" benzodiazepines appear to cause limited benzodiazepine effects and little or no behavioral tolerance. To evaluate behavioral and neurochemical effects of a partial agonist during chronic administration, we treated mice with Ro16-6028, 0.25, 1 and 4 mg/kg/day by implanted osmotic pumps, evaluating open-field activity and binding and function at the GABAA receptor. All three doses of Ro16-6028 caused dose-dependent decreases in vertical movements (rearing), and no tolerance was observed up to 14 days at any dose. In contrast, tolerance occurred to the effects of clonazepam at 7 days. Benzodiazepine receptor occupancy was essentially complete in all brain regions evaluated at doses of 1 and 4 mg/kg/day. Benzodiazepine binding in vivo at 0.25 mg/kg/day was transiently decreased in cortex at 7 days but was unchanged in any other brain region. Benzodiazepine binding in cortex in vitro was unchanged over time at any of the three doses, as were t-butylbicyclophosphorothionate binding and binding at the low- and high-affinity GABA sites measured by [3H]SR-95531. GABAA receptor function as determined by muscimol-stimulated chloride uptake was unchanged over 14 days of administration at Ro16-6028 doses of 0.25 and 4 mg/kg/day. Concentrations of Ro16-6028 were constant during administration at 1 and 4 mg/kg/day. These data indicate that chronic Ro16-6028 causes dose-dependent behavioral effects without the development of tolerance and that, despite substantial or complete benzodiazepine receptor occupancy, few effects occur at the GABAA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparative tolerance study of terfenadine-pseudoephedrine combination tablets and pseudoephedrine tablets in patients with allergic or vasomotor rhinitis

In this multicentre, double-blind, randomized, parallel group study, 315 patients with allergic or vasomotor rhinitis were treated on a twice daily dosing schedule with either a 60 mg terfenadine-120 mg pseudoephedrine hydrochloride combination or 120 mg pseudoephedrine hydrochloride (extended release) for 2 weeks. No clinically significant differences between the two groups were noted in body weight, temperature, respiration rate or blood pressure following the treatment period. An increase in mean heart rate of approximately 5 beats/min from entry to the final clinic visit was noted in both treatment groups. No clinically significant changes were noted in either treatment group when pre- and post-treatment electrocardiograms were compared. There were also no clinically significant alterations in laboratory values, which included serum chemistry, haematology and urinalysis, within or between either group. The adverse events profiles for both groups were similar. The most frequent adverse event was insomnia, in 40 (25.3%) patients given the terfenadine-pseudoephedrine combination and in 42 (26.8%) of those given pseudoephedrine. No unusual or unexpected adverse events were reported.     

The safety and tolerability of levodopa eye drops for the treatment of ocular disorders: A randomized first‐in‐human study

Myopia is the leading cause of low vision worldwide and can lead to significant pathological complications. Therefore, to improve patient outcomes, the field continues to develop novel interventions for this visual disorder. Accordingly, this first‐in‐human study reports on the safety profile of a novel dopamine‐based ophthalmic treatment for myopia, levodopa/carbidopa eye drops. This phase I, first‐in‐human, monocenter, placebo‐controlled, double‐blind, paired‐eye, multidose, randomized clinical trial was undertaken in healthy adult males aged 18–30 years (mean age 24.9 ± 2.7) at the University of Canberra Eye Clinic, Australia. Participants were randomly assigned to receive either a low (1.4 levodopa:0.34 carbidopa [μmoles/day], n = 14) or standard dose (2.7 levodopa:0.68 carbidopa [μmoles/day], n = 15) of levodopa/carbidopa eye drops in one eye and placebo in the fellow eye once daily for 4 weeks (28 days). Over this 4‐week trial, and after a 4‐month follow‐up visit, levodopa/carbidopa treatment had no significant effect on ocular tolerability and anterior surface integrity, visual function, ocular health, refraction/ocular biometry, and did not induce any non‐ocular adverse events. These results indicate that topical levodopa/carbidopa is safe and tolerable to the eye, paving the way for future studies on the efficacy of this novel ophthalmic formulation in the treatment of human myopia. The findings of this study have implications not only for the treatment of myopia, but in a number of other visual disorders (i.e., amblyopia, diabetic retinopathy, and age‐related macular degeneration) in which levodopa has been identified as a potential clinical intervention.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Preclinical data indicate that levodopa/carbidopa eye drops can safely inhibit the development of experimental myopia in animal models.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated whether levodopa/carbidopa eye drops are safe and tolerable to the human eye.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

In this phase I, first‐in‐human, monocenter, randomized, double‐blind, placebo‐controlled, multidose trial, levodopa/carbidopa eye drops were found to be safe and well tolerated in healthy adult males over a 4‐week period. Furthermore, no non‐ocular adverse events were reported.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

As topical administration of levodopa/carbidopa eye drops is well tolerated in humans, the efficacy of this novel ophthalmic treatment at inhibiting the development of myopia in patient populations can now be assessed. If found to be effective, this will provide a powerful new method for inhibiting the onset and development of the leading cause of low vision worldwide. This topical formulation may also provide a valuable tool in the treatment of other visual disorders shown to be responsive to levodopa therapy (i.e., amblyopia, diabetic retinopathy, and age‐related macular degeneration).     

羧甲基纤维素钠滴眼液联合普拉洛芬治疗糖尿病白内障术后干眼症的临床效果

目的探讨羧甲基纤维素钠滴眼液联合普拉洛芬治疗糖尿病白内障术后干眼症的临床效果。方法将我院86例糖尿病白内障术后干眼症患者随机分为对照组和联合治疗组,各43例。对照组采用羧甲基纤维素钠滴眼液治疗,联合治疗组采用羧甲基纤维素钠滴眼液联合普拉洛芬治疗。比较两组的干眼症状评分、临床疗效、泪膜破裂时间(BUT)、泪液分泌长度、角膜荧光素染色(FL)评分及泪液炎性因子水平。结果治疗前,两组的干眼症状评分比较,差异不具有统计学意义(P>0.05);治疗后,两组的干眼症状评分均降低,且联合治疗组显著低于对照组(P<0.05)。联合治疗组的治疗总有效率显著高于对照组(P<0.05)。治疗前,两组的BUT、泪液分泌长度和FL评分比较,差异不具有统计学意义(P>0.05);治疗后,联合治疗组的BUT、泪液分泌长度长于对照组,FL评分低于对照组(P<0.05)。治疗前,两组的IL-1β、IL-6、TNF-α水平比较,差异不具有统计学意义(P>0.05);治疗后,两组的IL-1β、IL-6、TNF-α水平下降,且联合治疗组低于对照组(P<0.05)。结论羧甲基纤维素钠滴眼液联合普拉洛芬治疗糖尿病白内障术后干眼症的临床效果显著,可减轻炎症反应。     

纳米晶眼药水对干眼症治疗作用的初步研究

目的 观察纳米晶眼药水对于眼症大鼠泪液分泌试验(Schirmer试验)、角膜荧光素染色、泪膜破裂时间(BUT)等的作用,探讨经纳米晶修饰后的玻璃酸钠眼药水(纳米眼药水)对大鼠干眼症的治疗作用.方法 建立大鼠干眼症动物模型,分别给予生理盐水、玻璃酸钠眼药水(普通眼药水)、纳米眼药水治疗,观察比较治疗前后不同时点的Schirmer试验、角膜荧光素染色及评分、BUT情况.结果 不同治疗组干眼症大鼠的Schirmer试验结果无统计学差异(P＞0.05).治疗第14天,纳米眼药水治疗组BUT时间明显长于其他两组,差异有统计学意义(P＜0.05);治疗21 d普通眼药水、纳米眼药水治疗组BUT均长于生理盐水组,差异有统计学意义(P均＜0.05).治疗第14天,纳米眼药水组角膜荧光素染色评分低于普通眼药水组及生理盐水组,差异均有统计学意义(P均＜0.05);治疗第21天,普通眼药水组角膜荧光素染色评分低于生理盐水组(P＜0.05),而纳米眼药水组角膜荧光素染色评分分别低于普通眼药水组(P＜0.05)及生理盐水组(P＜0.01).结论 纳米眼药水能提高玻璃酸钠眼药水治疗眼表上皮异常所致的干眼症的疗效.     

雷帕霉素联合环孢霉素A滴眼液对大鼠高危角膜移植排斥反应的作用

目的:观察雷帕霉素滴眼液眼局部应用对大鼠高危角膜移植免疫排斥反应的影响,并观察其与环孢霉素A联合应用的效果。方法:实验于2004-12/2005-03在辽宁医学院动物实验室完成,选用健康雄性SD受体大鼠50只及雌性Wistar供体大鼠23只。以SD角膜新生血管化大鼠为受体,建立大鼠高危穿透性角膜移植动物模型。①造模及移植术后40只受体大鼠进入结果分析,按随机数字表法分为4组,每组10只。对照组滴用滴眼液基质,雷帕霉素组滴用2g/L雷帕霉素滴眼液,环孢霉素A组滴用10g/L环孢霉素A滴眼液,各组均100μL/次;雷帕霉素 环孢霉素A组应用2g/L雷帕霉素滴眼液联合10g/L环孢霉素A滴眼液滴眼,各50μL/次。手术后第2天起术眼开始用药,4次/d,连续用药至排斥反应发生。②对角膜植片在裂隙灯下进行临床观测,混浊、水肿和新生血管3项指标评分之和为当日排斥反应指数,当排斥反应指数≥5时,或者植片混浊一项达到3时视为排斥反应发生,记录角膜植片存活时间。③角膜移植术后第14天各组随机抽取4只受体大鼠行角膜组织学检查。结果:40只受体大鼠进入结果分析。①各组受体大鼠角膜植片的存活时间比较:对照组、雷帕霉素组、环孢霉素A组及雷帕霉素 环孢霉素A组角膜植片的存活时间分别为(7.67±1.03,16.67±1.63,15.50±2.43,21.33±2.94)d,各用药组角膜植片的存活时间与对照组比较均显著延长(P<0.01);联合用药组优于单独用药组(P<0.01);雷帕霉素组与环孢霉素A组比较差异无显著性意义(P>0.05)。②各组受体大鼠角膜移植术后14d角膜的组织形态学变化:各用药组角膜植片炎细胞浸润、新生血管形成及水肿程度均明显轻于对照组,雷帕霉素与环孢霉素A联合用药组植片中央部未见炎性细胞浸润及新生血管。结论:2g/L的雷帕霉素滴眼液能显著延长高危角膜移植角膜植片的存活时间,联合应用10g/L的环孢霉素A滴眼液具有协同作用,治疗效果优于雷帕霉素或环孢霉素A单独用药。     

对比多种眼药治疗先天性上睑下垂术后相关性干眼症的临床疗效

目的比较妥布霉素眼膏单独使用及联合小牛血去蛋白提取物眼用凝胶、聚乙二醇滴眼液治疗先天性上睑下垂术后相关性干眼症的临床疗效。方法采用回顾性研究,对2012年8月~2016年5月于重庆医科大学附属儿童医院眼科诊断为先天性上睑下垂并接受额肌瓣悬吊术的术后住院患儿478例(640只眼)的临床资料进行统计分析。根据上睑下垂程度分为轻、中、重度3类,根据术后单独使用妥布霉素眼膏(A组),妥布霉素联合小牛血去蛋白提取物眼用凝胶(B组),妥布霉素联合聚乙二醇滴眼液分为三组(C组)。分别统计三组患儿术后第3天的症状评分、角膜荧光素染色评分(FL)、泪膜破裂试验(BUT)及基础泪液分泌试验(Sit)。结果对比A组,B组在轻、中、重3种不同程度的上睑下垂术后干眼有显著疗效(P0.05);而C组在轻、中程度的上睑下垂术后的干眼有明显疗效(P0.05);B与C组进行比较,显示前者在治疗中、重度上睑下垂术后疗效更好(P0.05)。结论相较于单独使用妥布霉素眼膏,额肌瓣悬吊术后使用妥布霉素眼膏联合小牛血去蛋白提取物眼用凝胶或聚乙二醇滴眼液对术后并发的干眼症具有明显优越性,且联合使用小牛血去蛋白提取物眼用凝胶更利于减轻干眼症症状及预防暴露性角膜炎。