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.     

Responsabilidad por pérdida de oportunidad asistencial en patología oncológica maligna en la medicina pública española

ObjectiveThe loss of chance in healthcare has been forcibly introduced in the adjudications pronounced in recent years. Our objective was to analyse the verdicts of guilt resulting from the loss of chance ordered by the Contentious-Administrative Court (i.e., in the public healthcare system), in which both the origin of the disease to be treated and the sequelae were oncological processes.MethodWe analysed 137 cancer-related court judgments from the Contentious-Administrative Court, which referred to the concept of loss of chance, issued in Spain up to May 2014.ResultsOf the 137 sentences, 119 (86.9%), were pronounced due to diagnostic error and 14 (10.2%) due to inadequate treatment. Since 2010, 100 sentences have been passed (73.0%), representing an increase of more than 170% with respect to the 37 (27.0%) ordered in the first six years of the study (from 2004 to 2009). Most of the patients (68.6%) died, predominantly from breast cancer and gynaecological cancer (24.1%), and gastrointestinal cancers (21.1%). These malignancies were the ones most often involved in the sentences.ConclusionsThe litigant activity due to loss of chance in oncological processes in the public health care has significantly increased in the last years. The judgments were mainly given because of diagnostic error or inadequate treatment.     

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。     

脊椎错位引起的代偿及其临床意义

脊柱的平衡在发生病理性变化时会打破，但人体有保持自我平衡的能力，脊柱必会发生一系列代偿性变化来重新建立平衡，这就是人体平衡系统作用的结果。当脊椎发生错位，即推拿医生最关心的脊椎错位时，脊柱内部将会发生怎样的代偿性变化及具有什么样的临床意义，下文将给予阐述。     

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。