An in vitro 3-dimensional Collagen-based Corneal Construct with Innervation Using Human Corneal Cell Lines.

Purpose: To develop a 3-dimensional corneal construct suitable for in vitro studies of disease conditions and therapies.

Design: In vitro human corneal constructs were created using chemically crosslinked collagen and chondroitin sulfate extracellular matrix and seeded with 3 human corneal cell types (epithelial, stromal, and endothelial) together with neural cells. The neural cells were derived from hybrid neuroblastoma cells and the other cells used from immortalized human corneal cell lines.

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.

Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness.

Ocular development after highly effective modulator treatment early in life.

Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor-tezacaftor-ivacaftor, correct the underlying molecular defect causing CF. HEMT decreases general symptom burden by improving clinical metrics and quality of life for most people with CF (PwCF) with eligible CFTR variants. This has resulted in more pregnancies in women living with CF.

Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients.

Objectives: Corneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation.

Harmonizing ophthalmic residency surgical training across Europe: A proposed surgical curriculum.

Background: One of the core aims of the European Union of Medical Specialists is to harmonize training across Europe by creating European Training Requirements for all medical specialties including Ophthalmology. The theoretical part is already defined by the EBO, however as ophthalmology also includes surgical skills, we herein propose a surgical minimum curriculum for ophthalmology residents in Europe.

Methods: National and international ophthalmic training curricula which are publicly available in English were reviewed and compared.

Survey of Ophthalmology Training Experiences Among Young Ophthalmologists in the Asia-Pacific.

Purpose: To describe ophthalmology training experiences across the Asia-Pacific (APAC).

Design: Survey study.

Methods: We utilized an anonymous online survey, which was previously validated and conducted in Europe, through Young Ophthalmologist leaders from the national member societies of the Asia-Pacific Academy of Ophthalmology (APAO) from September 2019 to July 2021.

Comparative analysis of European residency programs: benchmarking and harmonizing ophthalmology training in Europe.

Background/objectives: This study aims to benchmark the training programs of European ophthalmology residents.

Subjects/methods: An online survey, aimed at European ophthalmology residents in training and those within two years of completion, was sent through the national representatives of the European Society of Ophthalmology, Young Ophthalmologists section (SOE-YO). The study involved 214 subjects representing 36 of the 44 European countries offering ophthalmology training programs.

Graphene-Lined Porous Gelatin Glycidyl Methacrylate Hydrogels: Implications for Tissue Engineering.

Despite rigorous research, inferior mechanical properties and structural homogeneity are the main challenges constraining hydrogel's suturability to host tissue and limiting its clinical applications. To tackle those, we developed a reverse solvent interface trapping method, in which organized, graphene-coated microspherical cavities were introduced into a hydrogel to create heterogeneity and make it suturable. To generate those cavities, (i) graphite exfoliates to graphene sheets, which spread at the water/ heptane interfaces of the microemulsion, (ii) heptane fills the microspheres coated by graphene, and (iii) a cross-linkable hydrogel dissolved in water fills the voids.

Critical media attributes in E-beam sterilization of corneal tissue.

When ionizing irradiation interacts with a media, it can form reactive species that can react with the constituents of the system, leading to eradication of bioburden and sterilization of the tissue. Understanding the media's properties such as polarity is important to control and direct those reactive species to perform desired reactions. Using ethanol as a polarity modifier of water, we herein generated a series of media with varying relative polarities for electron beam (E-beam) irradiation of cornea at 25 kGy and studied how the irradiation media's polarity impacts properties of the cornea.

Advantages and Disadvantages of Using Magnetic Nanoparticles for the Treatment of Complicated Ocular Disorders.

Nanomaterials provide enormous opportunities to overcome the limitations of conventional ocular delivery systems, such as low therapeutic efficacy, side effects due to the systemic exposure, or invasive surgery. Apart from the more common ocular disorders, there are some genetic diseases, such as cystic fibrosis, that develop ocular disorders as secondary effects as long as the disease progresses. These patients are more difficult to be pharmacologically treated using conventional drug routes (topically, systemic), since specific pharmacological formulations can be incompatible, display increased toxicity, or their therapeutic efficacy decreases with the administration of different kind of chemical molecules.

Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds.

Collagen scaffolds, one of the most used biomaterials in corneal tissue engineering, are frequently crosslinked to improve mechanical properties, enzyme tolerance, and thermal stability. Crosslinkers such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) are compatible with tissues but provide low crosslinking density and reduced mechanical properties. Conversely, crosslinkers such as glutaraldehyde (GTA) can generate mechanically more robust scaffolds; however, they can also induce greater toxicity.

Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications.

Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking.

Combined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responses.

Inadequate supplies of donor corneas have evoked an escalating interest in corneal xenotransplantation. However, innate immune responses contribute significantly to the mechanism of xenograft rejection. We hypothesized that complement component C5 and TLR co-receptor CD14 inhibition would inhibit porcine cornea induced innate immune responses.

Toward electron-beam sterilization of a pre-assembled Boston keratoprosthesis.

Purpose: To evaluate the effects of electron-beam (E-beam) irradiation on the human cornea and the potential for E-beam sterilization of Boston keratoprosthesis (BK) devices when pre-assembled with a donor cornea prior to sterilization.

Methods: Human donor corneas and corneas pre-assembled in BK devices were immersed in recombinant human serum albumin (rHSA) media and E-beam irradiated at 25 kGy. Mechanical (tensile strength and modulus, and compression modulus), chemical, optical, structural, and degradation properties of the corneal tissue after irradiation and after 6 months of preservation were evaluated.

Electron Beam Sterilization of Poly(Methyl Methacrylate)-Physicochemical and Biological Aspects.

Electron beam (E-beam) irradiation is an attractive and efficient method for sterilizing clinically implantable medical devices made of natural and/or synthetic materials such as poly(methyl methacrylate) (PMMA). As ionizing irradiation can affect the physicochemical properties of PMMA, understanding the consequences of E-beam sterilization on the intrinsic properties of PMMA is vital for clinical implementation. A detailed assessment of the chemical, optical, mechanical, morphological, and biological properties of medical-grade PMMA after E-beam sterilization at 25 and 50 kiloGray (kGy) is reported.

Characterization of non-linear mechanical behavior of the cornea.

The objective of this study was to evaluate which hyperelastic model could best describe the non-linear mechanical behavior of the cornea, in order to characterize the capability of the non-linear model parameters to discriminate structural changes in a damaged cornea. Porcine corneas were used, establishing two different groups: control (non-treated) and NaOH-treated (damaged) corneas (n = 8). NaOH causes a chemical burn to the corneal tissue, simulating a disease associated to structural damage of the stromal layer.

In vitro susceptibility of microorganisms isolated from cold stored corneas: increased gentamicin-resistance in cornea banking.

Donor cornea contamination is one of the major risks for corneal transplants. The use of antibiotics in storage media remains as one of the most important security measurements to minimize the contamination risk in corneal preservation. Since antibiotic resistance among microorganisms have been rising gradually, it is important to gain knowledge about the antimicrobial susceptibility pattern for choosing the most suitable antimicrobial agents.

Successful development and clinical translation of a novel anterior lamellar artificial cornea.

Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue-engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin-agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior.

Effects of gamma radiation sterilization on the structural and biological properties of decellularized corneal xenografts.

To address the shortcomings associated with corneal transplants, substantial efforts have been focused on developing new modalities such as xenotransplantion. Xenogeneic corneas are anatomically and biomechanically similar to the human cornea, yet their applications require prior decellularization to remove the antigenic components to avoid rejection. In the context of bringing decellularized corneas into clinical use, sterilization is a crucial step that determines the success of the transplantation.

Finding an Optimal Corneal Xenograft Using Comparative Analysis of Corneal Matrix Proteins Across Species.

Numerous animal species have been proposed as sources of corneal tissue for obtaining decellularized xenografts. The selection of an appropriate animal model must take into consideration the differences in the composition and structure of corneal proteins between humans and other animal species in order to minimize immune response and improve outcome of the xenotransplant. Here, we compared the amino-acid sequences of 16 proteins present in the corneal stromal matrix of 14 different animal species using Basic Local Alignment Search Tool, and calculated a similarity score compared to the respective human sequence.

Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Results From the INCREMENT Cohort.

Background: There is little information about the efficacy of active alternative drugs to carbapenems except β-lactam/β-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems.

Methods: A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed.