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.     

(-)-Epigallocatechin-3-gallate,reduces corneal damage secondary from experimental grade II alkali burns in mice

Background

Since recent reports have shown that (-)-Epigallocatechin-3-gallate (EGCG) could be used for treating proliferative and inflammatory disorders, we explored its use for the management of corneal chemical burns.

Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

103例角膜溃疡的病因和病原及药物敏感试验的统计分析

对１９９５年１—１２月间我院门诊１０３例角膜溃疡的病因、病原和药物敏感试验进行统计分析。病因：外伤５９例（５７．２８％），继发感染３４例（３３．０１％），原因不明８例（７．７７％），戴接触镜２例（１．９４％）。病原：真菌３５例（３３．９８％），绿脓杆菌１８例（１７．４８％），金黄色葡萄球菌１５例（１４．５６％），表皮葡萄球菌９例（８．７４％），淋球菌２例（１．９４％）。对１９例真菌性角膜溃疡同时进行细菌培养，有７例为混合感染，占３６．８４％。对几种主要检出菌的药物敏感试验表明：它们对普通抗菌素均可产生一定的耐药性     

MMP-2、TIMP-2与碱烧伤后角膜新生血管形成的实验研究

目的:探讨基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-2组织型抑制剂(TIMP-2)在碱烧伤大鼠角膜新生血管(CNV)形成中的表达和意义。方法:采用碱烧伤大鼠角膜建立CNV模型,摘除角膜作病理切片,多形核白细胞(PMN)记数;免疫组化法检测MMP-2、TIMP-2的表达。结果:烧伤后1d角膜缘PMN开始增多,到CNV7d组PMN增加最明显,此后逐渐减少;免疫组化显示:MMP-2在CNV中阳性表达逐渐增加,于7d表达最明显,此后随炎性细胞的减少而减弱,21d后几乎无表达;TIMP-2则于早期变化不明显,7d表达开始升高,14d达高峰。结论:烧伤后CNV形成早期,MMP-2活性增高,继而TIMP-2表达增加,使MMP-2活性受抑,基底膜降解受阻,新生血管延伸停滞;CNV形成中,MMP-2的表达增加,并与角膜的炎性反应程度一致,PMN浸润可能是CNV形成的关键因素。     

聚合酶链反应检测铜绿假单胞菌感染性角膜溃疡的实验研究及临床应用

目的：探索聚合酶链反应（PCR）技术对铜绿假单胞菌感染性角膜溃疡快速诊断的可行性。优越性及其在临床应用中的价值。方法：建立PCR检测标准铜绿假单胞菌方法，对兔铜绿假单胞菌感染性角膜溃疡模型研究并应用于临床，并与细菌培养做比较。结果：铜绿假单胞菌扩增出一条长504bp的阳性条带，其他常见细菌，人和兔正常角膜组织均为阴性，动物模型PCR敏感性为93.8%。特异性为100.0%；细菌培养敏感性为68.7%。特异性为93.7%。临床标本PCR阳性率为66.7%；细菌培养阳性率为38.1%。结论：PCR技术对快速检测实验室和临床标本中的铜绿假单胞菌具有重要的应用价值。     

激光上皮下角膜磨镶术后角膜上皮瓣临床观察

目的 观察及探讨准分子激光上皮下角膜磨镶术(Laser subepithel ialkeratomileusis，LASEK)后，角膜上皮瓣的成活率及其影响因素。方法 对行LASEK治疗的42例(80眼)于术后1、2、3天，1、2、3、4周在裂隙灯显微镜下进行角膜上皮瓣的观察。结果 34例(68眼)，角膜上皮瓣成活，成活占85％(68／80)；未成活8例(12眼)，未成活占15％(12／80)。结论 LASEK术后角膜上皮瓣成活率的高低，决定着LASEK的临床疗效，影响其成活的因素是多方面的。其中角膜上皮瓣边缘不整齐、破裂、对位不良、操作时间过长可能是其主要原因。     

481例住院角膜病统计分析

本文统计分析１９８５－１９９０年间我院眼科４８１例（５６９只眼）住院角膜病患者的病种分布和致盲原因。调查结果表明，发病性别男多于女（２：１），发病年龄以２１－５０岁为多，５３．６％，最常见及致盲率高的为角膜炎症和外伤，其中病毒性角膜炎最多（３３．９％），细菌性角膜溃疡致盲率最高（４２．２％），角膜外伤居第二。分析表明，今后工作的重点是预防和治疗角膜炎症和外伤。     

闭合式小切口手法碎核折叠式人工晶体植入联合穿透性角膜移植术

目的探讨利用小切口手法碎核技术,选择性地对同时患有角膜病变和白内障的病例施行闭合式白内障摘除人工晶体植入联合穿透性角膜移植（三联术）的临床效果。方法选择2001年1月至2005年12月在本中心就诊的12例（13只眼）同时患有角膜病变和白内障的病人,在局麻下先施行3mm弦长、180度圆弧的巩膜隧道切口,手法碎核（三切核）、植入6.5mm直径的折叠式人工晶体后,用负压环钻切除病变角膜组织,立即用连续缝合法将植片缝于植床。术后常规全身应用抗生素和皮质激素,局部滴用免疫抑制剂（环孢霉素A）滴眼剂2～6个月;最后随访时间为2～72个月,平均22个月。结果本组12例（13只眼）无一例在术中发生并发症。术后1例发生浅前房,3d后前房恢复正常,但虹膜周边局部前粘;出院时,眼压均在正常范围。1例在术后5个月时发生植片自溶,再次行角膜移植,半年后植片血管化,放弃治疗。3例术后1年发生免疫排斥反应;经再次局部应用免疫抑制剂2～3个月后角膜恢复透明。最后随访时,9例植片透明,3例在植缘有少量新生血管;瞳孔均居中,基本为圆形;人工晶体位置不偏,后囊明显混浊1例,施行YAG激光后囊膜切开。无一例发现囊口收缩或明显的囊口纤维化。最后随访时矫正视力0.04～0.8,平均0.4。结论选择性地对同时患有角膜病变和白内障的病人采用闭合式小切口手法碎核三联术,术式简化、术时短;术中并发症少、风险小、安全;可以尽早地恢复病眼的视力。