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.

Protective effect of bromelain on corrosive burn in rats

IntroductionIn some cases, the tongue and oesophagus tissues are damaged by the corrosive burn. Surgical interventions may cause scar formation, and severe burns treatment methods are limited. This study aims to investigate bromelain, a phytotherapeutic product, on the corrosive burn as a non-surgical option and as an adjunctive therapy, insofar as the treatment of corrosive wounds is not limited only to the treatment of oxidative stress and inflammatory reactions.MethodsOn the tongues of Wistar albino rats, chemically produced oral ulcers were created by topical application of NaOH (40%) solution, and in the distal oesophagus same mixture was applied to produce a corrosive oesophageal burn. For a week, they were treated orally by bromelain (100 mg/kg/day) or saline solution. At the end of seven days, animals were decapitated to remove the tongue and oesophagus, and blood samples were collected to obtain serum. Myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) concentrations were measured in serum, and luminol and lucigenin chemiluminescence (CL) were measured in tissue samples.ResultsMDA and CL values were significantly increased, and GSH levels in tissue significantly decreased due to the corrosive burns. Saline treated corrosive burn group measured higher in the serum cytokines in according to the control group.ConclusionsBromelain administration decreased oxidant and inflammatory parameters and increased antioxidant levels in NaOH-induced corrosive burns. Thus, we concluded that bromelain may protect the tongue and oesophagus tissues with its anti-inflammatory and antioxidant effects.     

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.     

The best strategy for red blood cell transfusion in severe burn patients,restrictive or liberal: A randomized controlled trial

IntroductionAlthough blood transfusion is common in burns, data are lacking in appropriate transfusion thresholds. It has been reported that a restrictive blood transfusion policy decreases blood utilization and improves outcomes in critically ill adults, but the impact of a restrictive blood transfusion policy in burn patients is unclear. We decided to investigate the outcome of decreasing the blood transfusion threshold.Material and methodsEighty patients with TBSA > 20% who met our inclusion criteria were included. They were randomly divided into control and intervention groups. The intervention group received packed cells only when Hemoglobin declined to less than 8 g/dL at routine laboratory evaluations. While the control group received packed-cell when hemoglobin was declined to less than 10 g/dl. The total number of the received packed cell before, during and after any surgical procedure was recorded. The outcome was measured by the evaluation of the infection rate and other complications.ResultThe mean hemoglobin level before transfusion was 7.7 ± 0.4 g/dL in the restrictive group and 8.8 ± 0.7 g/dL in the liberal group. The mean number of RBC unit transfusion per patient in the restrictive group was significantly lower than the traditional group (3.28 ± 2.2 units vs. 5.9 ± 3.7 units) (p-value = 0.006). The total number of RBC transfused units varied significantly between the two groups (p-value = 0.014). The number of transfused RBC units outside the operation room showed a significant difference between groups (restrictive: 2.8 ± 1.4 units vs. liberal: 4.4 ± 2.6 units) (p = 0.004). We did not find any significant difference in mortality rate or other outcome measures between groups.ConclusionApplying the restrictive transfusion strategy in thermal burn patients who are highly prone to all kinds of infection, does not adversely impact the patient outcome, and results in significant cost savings to the institution and lower rate of infection. We conclude that the restrictive transfusion practice during burn excision and grafting is well tolerated and effective in reducing the number of transfusions without increasing complications.Clinical Trial Registration ReferenceIRCT20190209042660N1.     

生物羊膜覆盖治疗早期重度眼表烧伤

目的探讨生物羊膜在早期重度眼表烧伤中的临床疗效。方法对17例(20眼)重度眼表烧伤患者施行生物羊膜覆盖术。随访3~7月,观察临床疗效。结果术后全部患者均保存了眼球。角膜恢复透明11眼,角膜斑翳7眼,角膜白斑2眼,角膜新生血管9眼,睑球粘连1眼。12眼视力提高>3行。无急性排斥反应和继发感染发生。结论生物羊膜覆盖是治疗早期重度眼表烧伤一种安全有效的方法。     

MEBO治疗口腔、咽、食管烧伤临床观察

目的:探讨口腔、咽、食管烧伤的治疗方法。方法:对2000年3月-2005年12月,采取口服湿润烧伤膏(MEBO)治疗的25例患者进行回顾性资料总结。结果:25例病人均治愈,无创面感染、食管狭窄、腹泻等并发症。结论:MEBO对口腔、咽、食管等上消化道部位黏膜烧伤疗效确切,方法简单易行。     

角膜碱烧伤房水一氧化氮及一氧化氮合酶变化

目的探讨角膜碱烧伤后房水一氧化氮（NO）与炎症反应的关系。方法用健康家兔动态观察对照组、实验组和对侧眼组眼内炎症反应及房水一氧化氮合酶（NOS）和NO2^-／NO3^-的活性。结果角膜碱烧伤后炎症反应与房水NOS和NO活性呈动态变化，实验组明显高于对侧眼组，且两组均高于对照组。结论房水NO的变化与角膜碱烧伤后的眼内炎症反应密切相关。     

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