立他司特：黏附因子抑制剂类干眼症新药

立他司特（Lifitegrast）是一种新的细胞间黏附因子的抑制剂,可以通过阻断细胞间黏附分子-1和整合素蛋白淋巴细胞功能相关抗原-1之间的结合起效。2016年7月,美国食品药品管理局（FDA）正式批准了5%立他司特滴眼剂（商品名Xiidra^TM）的申请。该药的临床试验主要包括针对干眼症患者的1个为期12周的II期临床试验和3个为期12周的III期临床试验,研究结果充分证明了该药的有效性和安全性。立他司特是FDA批准的第一个可以改善和治疗干眼症症状的新药,其他类似药物只有环孢素,在不久的将来其临床应用会更加广泛。     

Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials

Objective: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED).

Research design and methods: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed.

Main outcome measures: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0–4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0–4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0–100).

Results: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05–0.65; p?=?0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10–0.38; p?=?0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35–24.33; nominal p?=?0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51–16.70; p?<?0.0001).

Limitations: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed.

Conclusions: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED.     

异黄酮片治疗更年期女性干眼症的临床研究

目的 观察异黄酮对更年期女性干眼症的临床疗效.方法 收集本院2012年1月～2013年6月收治的更年期女性干眼症患者218例,随机分成采用常规治疗的对照组和采用异黄酮治疗的观察组,每组各109例,比较两组临床疗效.结果 观察组的总有效率为72.5％,显著高于对照组的49.5％（P＜0.05）;两组患者治疗前后体内血清雌激素的水平均未发生显著性变化（P＞0.05）;对照组和观察组的不良反应发生率分别为2.8％和1.8％,差异无统计学意义（P＞0.05）.结论 异黄酮治疗更年期女性干眼症临床效果显著,不良反应较少,值得临床推广应用.     

Patent Evaluation: Purification and gene cloning of the somatostatin receptor

5-Benzyl-5-methyl-3-phenylhydantoin derivatives are claimed as antagonists of the interaction between the lymphocyte function-associated antigen (LFA-1) and the intercellular adhesion molecule-1 (ICAM-1). Such antagonists have a broad therapeutic potential in the treatment of inflammatory diseases such as asthma and as immunosupressants.     

Emerging drugs for the treatment of dry eye disease

Introduction: Dry eye disease (DED) is a common, age-related ocular condition that in its mildest forms causes bothersome symptoms of ocular discomfort, fatigue, and visual disturbance that interfere with quality of life and in its more severe forms causes chronic pain and fluctuating vision. Though it is highly prevalent and costs billions of dollars to manage, current treatments have largely been inadequate, making it a frustrating condition, both for physicians and patients alike.

Areas covered: This article will cover the recently discovered pathophysiology of DED that has prompted investigators to explore new molecules that target the core mechanisms that drive DED. These include anti-inflammatory/immune-modulatory drugs, secretagogues, lubricant, hormones, and autologous serum. Their potential mechanism of action and data from recent trials on efficacy/safety will be reviewed.

Expert opinion: The emerging drugs have a vast range of putative mechanisms of action that may not only provide symptomatic relief but may potentially break the vicious cycle of DED and provide long-lasting cure. Current and future research may change our perspective on DED and redefine its treatment algorithms.     

Work productivity loss in patients with dry eye disease: an online survey

Abstract

Objective:

To assess the impact of dry eye disease (DED) on productivity.     

Safety and efficacy of autologous serum eye drop for treatment of dry eyes in graft-versus-host disease

Purpose: To evaluate the treatment of autologous serum eye drops (ASED) on dry eyes in patients with graft-versus-host disease (GVHD).

Methods: A retrospective chart review of 35 patients with a history of ocular GVHD following hematopoietic stem cell transplantation that used ASED to alleviate dry eye symptoms was performed. Patients were categorized into three different groups. If patients had available ophthalmic data before and after starting treatment was group 1 (n?=?14), had available ophthalmic data after starting treatment in group 2 (n?=?10) and had available ophthalmic data before treatment or did not have any data after starting treatment in group 3 (n?=?11). Data were collected on patient’s age, gender, primary diagnosis, visual acuity and fluorescein corneal staining were collected on individual eyes in order to evaluate the efficacy of the ASED on alleviating dry eye-related signs and symptoms.

Results: No adverse ocular effect from the ASED was found in our series (except one fungal keratitis). All patients reported either improvement (55%) or stability (45%) in their ocular symptoms upon the use of ASED. In patients with available data before and after starting treatment, the corneal staining score improved by a median of 1 (p?=?0.003) and the LogMAR visual acuity had a non-significant improvement.

Conclusion: In our study, ASED used by patients with ocular GVHD were both safe and effective. ASED should be considered in patients with GVHD who suffer from dry eyes.     

眼干燥综合征相关因素分析及临床干预的效果

目的探讨眼干燥综合征(干眼症)的相关因素和临床干预效果。方法干眼症患者218例,随机均分为干预组(A组,常规给予病因治疗、泪液治疗及系统的临床干预)和对照组(B组,仅常规给予病因治疗和泪液治疗),比较两组治疗2周后的泪液功能试验(SIT)、泪膜破裂时间(TBUT)、角膜荧光染色检查(FL)和自我测评等指标。结果视频终端综合征或看书为干眼症相关的主要因素,占45.41%(99/218),其次分别为闭经或泪腺萎缩老化占37.16%(81/218),眼表手术或用药占33.49%(73/218),户外工作或户外运动者占29.36%(64/218),佩戴隐形眼镜占21.56%(47/218),饮食结构(维生素A缺乏)占7.34%(16/218)。A组SIT、TBUT、FL和自我测评评分均明显高于B组﹙P<0.05﹚。结论干眼症的相关因素是多方面的,科学、有效的实施临床干预能减轻干眼症患者的症状。     

物理疗法在睑板腺功能障碍所致干眼治疗中的应用效果观察

目的：探讨物理疗法治疗睑板腺功能障碍所致干眼的疗效。方法2010年1月-2012年5月门诊确诊的68例睑板腺功能障碍引起的蒸发过强型干眼症,随机分配到对照组和观察组,各34例。对照组患者接受眼部药物治疗,观察组药物治疗配合眼部物理疗法治疗,通过观察两组患者治疗后临床症状的变化来评定治疗效果。结果对照组总有效率为67.65%,观察组总有效率为94.12%,两组对比差异具有统计学意义（P＆lt;0.05）。结论物理疗法能有效改善睑板腺功能,提高蒸发过强型干眼症的治疗效果,值得推广。     

Ciclosporin use in dry eye disease patients

Background: Dry eye disease is one of the most commonly encountered conditions in eye care, and inflammation is a frequent finding. Ciclosporin has long been used systemically to decrease the deleterious effects of inflammation. Ciclosporin is a calcineurin inhibitor that acts by primarily blocking the action of T cells, decreasing the release of pro-inflammatory cytokines, and preventing the apoptosis of goblet cells. Objective: This article reviews the clinical trials and safety profile of an ophthalmic preparation of ciclosporin in the treatment of dry eye. Results/conclusion: Clinical trials have demonstrated that ciclosporin minimizes the signs and symptoms of dry eye disease and is not associated with any significant systemic or ocular adverse reaction.     

干眼症相关因素的初步研究

目的对干眼症的相关因素进行分析,以指导干眼症的预防与诊治。方法对2008年6月～2010年5月于我院眼科门诊以干眼症状就诊的患者335例进行Schirmer test检测及泪膜破裂时间(BUT)检查,对患者性别、出现症状的季节、屈光不正与否及每天视屏幕的时间等因素进行分析。结果 335例患者中确诊为干眼症的患者为195例,确诊为干眼症的比率在春季最高;屈光不正患者较非屈光不正患者中确诊为干眼症的比率高;每日注视屏幕时间长的患者确诊为干眼症的比率较高。结论综合考虑干眼症的相关因素有助于干眼症的预防与诊治。     

使用电脑对干眼症的影响

目的探讨使用电脑对干眼症的发病和症状加重是否会有影响。方法在山西省汾阳学院师生中就干眼症的8个症状、上机时间与干眼程度、用药情况对干眼症的影响进行为期2个月的问卷调查。结果得到问卷310份,使用电脑的人至少会有一种干眼症的症状,多数人忽略,少数人就医或自买药物;上机时间长,眼干症状重;     

睑板腺按摩联合药物治疗睑板腺功能障碍型干眼症的疗效观察

目的观察睑板腺按摩联合药物治疗睑板腺功能障碍型干眼症的临床疗效。方法选取洪雅县人民医院五官科2017年1月-2018年12月收治的睑板腺功能障碍型干眼症患者82例,按就诊顺序分为治疗组和对照组各41例。对照组采用玻璃酸钠滴眼液滴眼联合中药治疗,治疗组在对照组的基础上,同时采用睑板腺按摩治疗。治疗后2组评定治疗效果,并观察2组不良反应发生情况。结果治疗过程中,治疗组退出观察2例,对照组因意外妊娠退出观察1例。治疗组总有效率为89.74%高于对照组的67.50%(χ~2=5.79,P<0.05)。2组均无明显不良反应。结论功能障碍型干眼症在常规运用玻璃酸钠滴眼液及中药治疗的基础上,同时采用睑板腺按摩联合治疗疗效较好,在临床工作中有较强的实用性及推广价值。     

眼科门诊干眼症的流行病学调查及危险因素分析

目的探讨眼科门诊干眼症患病状况及相关危险因素。方法选取2008年2月～2012年2月本院1696例眼科门诊患者进行问卷调查,行特异性检查、裂隙灯检查、角膜荧光素染色。对干眼症确诊者依1∶2配比手段展开病例对比,分析相关危险因素。结果 1696例患者中,188例（占11.08%）为干眼症,女136例（占72.34%）,男52例（占27.66%）;〈20岁6例（占3.19%）,20～40岁79例（占42.02%）,〉40岁103例（占54.79%）,113例（占60.11%）长期使用抗生素、激素滴眼液。结论干眼症患者在性别、年龄等方面差异较大,而长期使用抗生素、激素滴眼液可能是干眼症的危险因素。     

玻璃酸钠滴眼液对轻中度干眼病患者角膜表面规则性的影响

目的评价玻璃酸钠滴眼液对干眼病患者的角膜表面规则性的影响。方法应用DICON——CT200角膜地形图仪检测滴玻璃酸钠滴眼液前后33例（64眼）干眼病患者的角膜表面规则指数（surface regularity index,SRI）表面不对称指数（surface asymmetry index,SAI）及角膜预测视力（potential visual acuity,PVA）的变化进行观察。结果干眼病患者的SRI、SAI、PVA值及散光度分别为1.32±0.44、1.11±1.43、20/30.12±20/11.93及2.45±1.9;滴玻璃酸钠滴眼液后SRI、SAI、PVA值分别0.83±0.21、0.59±0.31、20/21.03±20/5.12及1.87±1.13。干眼病患者在滴玻璃酸钠滴眼液后SRI、SAI和散光度均明显降低,而PVA则明显升高。滴玻璃酸钠滴眼液前干眼病患者的角膜地形图43.8%为不规则形,应用玻璃酸钠滴眼液后不规则形降为29.7%。结论SRI和SAI可作为诊断干眼病的客观指标并可用于评价干眼病的严重程度及玻璃酸钠滴眼液的疗效。璃酸钠滴眼液可改善干眼病患者的角膜表面光滑度。     

维生素A棕榈酸酯眼用凝胶预防及治疗LASIK术后干眼症

目的探讨维生素A棕榈酸酯眼用凝胶预防及治疗近视患者LASIK术后干眼症的疗效。方法对466例(932只眼)拟行LASIK治疗的近视患者做术前泪膜相关筛查,通过术前筛查排除严重的干眼症患者,对轻、中度干眼患者通过围手术期维生素A棕榈酸酯眼用凝胶点眼治疗,非干眼患者术后应用维生素A棕榈酸酯眼用凝胶点眼预防干眼发生。观察术后1周及1、3、6个月的干眼症发生率。结果术前诊断为轻、中度干眼症并术前用药的155只眼于术后7 d及1、3、6个月做泪膜相关检查并诊断为干眼症的眼数分别为69只眼(44.6%)、52只眼(33.4%)、26只眼(16.6%)、7只眼(4.6%)。术前筛查已排除干眼症的761只眼于术后开始用药,术后7 d及1、3、6个月检查符合干眼症诊断的分别为244只眼(32.1%)、145只眼(19.0%)、64只眼(8.4%)、12只眼(1.6%)。结论采取术前筛查和围手术期药物干预是预防和治疗LASIK术后干眼症的有效措施;维生素A棕榈酸酯眼用凝胶可以有效预防及治疗LASIK术后干眼症。     

羧甲基纤维素钠滴眼液治疗2型糖尿病合并白内障术后干眼症的有效性及安全性

目的 分析羧甲基纤维素钠滴眼液治疗2型糖尿病合并白内障术后干眼症的有效性及安全性.方法 150例2型糖尿病合并白内障患者,根据治疗方法不同分为对照组和观察组,每组75例.对照组予以胰岛素+妥布霉素地塞米松滴眼液治疗,观察组在对照组治疗基础上+羧甲基纤维素钠滴眼液治疗.比较两组患者治疗效果、不良反应发生情况以及治疗前后的...     

Binding and Internalization of an LFA-1-Derived Cyclic Peptide by ICAM Receptors on Activated Lymphocyte: A Potential Ligand for Drug Targeting to ICAM-1-Expressing Cells

Purpose. The interaction of cell-adhesion molecules LFA-1/ICAM-1 is critical for many inflammatory and immune responses. Blockades of this interaction using antibodies or peptide analogs are being developed as therapeutic approaches for inflammatory and autoimmune diseases. The aim of this study is to examine the binding and internalization mechanisms of LFA-1 peptide [cLAB.L or cyclo-(1,12)-PenITDGEATDSGC] mediated by ICAM receptors on the surface of lymphocytes. Methods. The binding and internalization of cLAB.L were evaluated using fluorescence-labeled cLAB.L on activated Molt-3 cells, measured by flow cytometry. Confocal fluorescence microscopy was also used to image the distribution of peptide binding and internalization. Results. The binding of FITC-cLAB.L exhibited bimodal cell distribution and was enhanced by Ca²⁺ and Mg²⁺. Marked differences in peptide binding were found between 37 and 4°C, as well as between activated and non-activated cells. Unlabeled peptide, low temperature, and the absence of cell activation suppress the peptide binding. The presence of peptide in the cytoplasm was detected in 37 but not 4°C binding. Peptide cLAB.L inhibited the binding of monoclonal antibodies to domain D1 of ICAM-1 and domain D1 of ICAM-3. Conclusions. Peptide cLAB.L can bind to the D1-domain of ICAM-1 and, to a lesser extent, to ICAM-3 on activated T-cells. Peptide binding indicates responses to the multiple and dynamic states of activated receptor ICAMs; this peptide may also be internalized by ICAM receptors on T-cells. This work suggests that cLAB.L has a therapeutic potential to target drugs to ICAM-1 expressing cells including autoreactive lymphocytes and inflamed tissues.