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.     

Overview of Protein‐Based Biopolymers for Biomedical Application

Biopolymers are playing a vital role in biomedical applications. Among them, protein‐based biopolymers are utilized for the fabrication of tissue‐engineering constructs, therapeutic molecule delivery carriers, emulsifiers, and food packaging materials. Wide ranges of proteins are extracted from animal or plant sources and are being utilized for the fabrication of scaffolds for regenerative tissue‐engineering application. Here, an overview about the protein structure, extraction procedure, solubility, and various formulation‐based proteins found in the literature are discussed. Biopolymers display several advantages such as biocompatibility and degradability by enzymes. Methods to overcome the disadvantages of these proteins such as immunogenicity, antigenicity, and solubility are reported. Various crosslinking reagents specific to protein chemistry are discussed as well.     

Endoscopic transnasal canaliculorhinostomy for refractory common canalicular obstruction with an unidentifiable lacrimal sac

AIM: To compare the safety and efficacy of conventional versus accelerated (9 mW/cm2) CXL in progressive keratoconus at the 2-year follow-up. METHODS: In this prospective study, consecutive progressive keratoconus patients were randomized to receive either conventional CXL (CCXL) or accelerated CXL (ACXL, using hydroxypropyl methylcellulose-assisted riboflavin imbibition for 10min) at 9 mW/cm2. Visual, refractive, keratometric, topographic, and aberrometric outcomes and stromal demarcation line depth (DLD) measurements were compared at the end of a 2-year follow-up. RESULTS: Thirty-two eyes from 32 patients in the CCXL and 27 eyes from 27 patients in the ACXL groups completed 2-year follow-ups. At 2 years post-CXL, both uncorrected and corrected visual acuities improved significantly in both groups. The improvements in keratometric readings, flattening rate (flattening of the Kmax more than 1D), 3 topographic indices, and vertical coma were significantly better in the CCXL group compared to the ACXL group (P<0.05). The DLD as measured by anterior segment optical coherence tomography or in vivo confocal microscopy was better detectable and significantly deeper in the CCXL group compared to the ACXL group. The deeper DLD was found to be significantly correlated with improvements in the mean keratometry measurements. Progression was noted in 11.1% of eyes in the ACXL group, whereas progression was not observed in any patient eye in the CCXL group. CONCLUSION: In this prospective randomized study, ACXL was less effective in halting the progression of keratoconus at a 2-year follow-up compared to CCXL.     

SMILE联合快速角膜交联术后角膜光密度的早期临床观察

目的 观察飞秒激光小切口角膜基质透镜取出术联合快速角膜胶原交联术(SMILE Xtra)对角膜光密度的影响。 方法 收集2017年3月至2019年7月在济南明水眼科医院矫正近视及近视散光的患者78例,纳入右眼数据(78眼)进行分析,根据手术方式分为SMILE Xtra组和SMILE组,其中SMILE Xtra组39例(39眼),SMILE组39例(39眼),分别在术前和术后3个月对两组患者的角膜光密度值进行随访。应用Pentacam三维眼前节分析系统测量角膜光密度值,根据软件分析,以角膜顶点为中心,获取0~2 mm、2~6 mm及6~10 mm直径范围角膜光密度平均值,同时获取角膜前120 μm、中间基质层及后60 μm的光密度平均值。 结果 SMILE Xtra组和SMILE组在术后3个月时78眼(100%)UCVA均达到术前预期矫正视力。SMILE Xtra组术后整体角膜及角膜0~2 mm、2~6 mm直径范围的光密度值均较手术前显著增高,且变化有统计学意义(P<0.001)。逐层分析显示术后前120 μm的数值均显著高于中部及后部角膜。SMILE组术后角膜各个直径范围的光密度值与术前差异有统计学意义(P<0.05)。角膜中部角膜组织及后60 μm的光密度值在手术前后变化有统计学意义(P<0.05)。SMILE Xtra组手术后3个月角膜光密度在0~2 mm、3~6 mm、7~10 mm和前120 μm的数值均高于SMILE组,差异有统计学意义(P<0.05)。两组角膜光密度值的变化量与等效球镜度、角膜中央厚度、角膜曲率及角膜上皮厚度变化量均无明显相关性(P>0.05),与年龄呈负相关(r=-0.542, P=0.01)。 结论 SMILE Xtra组术后早期角膜光密度增加,透明度下降,但只在手术操作区域内发生变化。     

Study on Characteristics of Acellular Bovine Pericardium Crosslinked with Genipin

The study used a naturally occurring crosslinking reagent-genipin to chemically modify acellular bovine pericardium, prepare cardiac valve tissue engineering scaffold material,and evaluated genipin crosslinked acellular matrix of bovine pericardium by investigating the physical and chemical properties of the tissues, such as the surface properties, crosslinking characteristics, mechanical properties, resistance to enzymatic capacity in vitro, and hemolysis tests. The results showed that acellular bovine pericardium matrix crosslinked with genipin was strong hydrophilicity, high crosslinking index, and stable structure, which can maintain good mechanical properties. As a kind of scaffold material for valve tissue engineering, it has wide application prospect.     

Parameter Study on the Preparation of UV Depth‐Cured Chemically Resistant Polysulfone‐Based Membranes

Polysulfone‐based membranes with excellent chemical resistance and a wet thickness up to 200 μm are obtained via UV curing of unmodified polymers after careful tuning of the photoinitiating system and the crosslinker structure. Combinations of photoinitiator and crosslinker are studied in depth, followed by a characterization of the formed macromolecular structure. The performance of the resulting membranes is then evaluated through long‐term immersion in solvents. Classical depth‐curing acyl phosphine oxide‐based photoinitiators in combination with a pentaacrylate crosslinker are found to be the optimal system.

     

1,4‐Bisbenzil: Visible‐Light‐ and Heat‐Assisted Crosslinking of Polystyrene Films

Polystyrene (PS) film containing 1,4‐bisbenzil is efficiently crosslinked in two steps. In the first step, visible light (λ > 400 nm) causes molecular oxygen to insert between two carbonyl groups of one of the 1,2‐dicarbonyl groups. The peroxide is subsequently decomposed by absorption of another photon, forming acyloxy radicals, which add to the aromatic ring of the PS chain. The remaining 1,2‐dicarbonyl group is then photoperoxidized to form PS with pendant benzoyl peroxide moieties. In the second step, pendant benzoyl peroxide groups are decomposed thermally to form acyloxy macroradicals responsible for the crosslinking. Crosslinking proceeds simultaneously with degradation. Finally, the gel content in the film may exceed 80 wt%.

     

Aggregation and Crosslinking of Poly(N,N‐dimethylacrylamide)‐b‐pullulan Double Hydrophilic Block Copolymers

The self‐assembly of polymers is a major topic in current polymer chemistry. In here, the self‐assembly of a pullulan based double hydrophilic block copolymer, namely pullulan‐b‐poly(N,N‐dimethylacrylamide)‐co‐poly(diacetone acrylamide) (Pull‐b‐(PDMA‐co‐PDAAM)) is described. The hydrophilic block copolymer induces phase separation at high concentration in aqueous solution. Additionally, the block copolymer displays aggregates at lower concentration, which show a size dependence on concentration. In order to stabilize the aggregates, crosslinking via oxime formation is described, which enables preservation of aggregates at high dilution, in dialysis and in organic solvents. With adequate stability by crosslinking, double hydrophilic block copolymer (DHBC) aggregates open pathways for potential biomedical applications in the future.