Multimodal Approach in Dry Eye Disease Combining In Vivo Confocal Microscopy and HLA-DR Expression.

Purpose: The purpose of this study was to determine the association between corneal images provided by in vivo confocal microscopy (IVCM) with clinical parameters and conjunctival expression of HLA-DR antigen in patients with dry eye disease (DED).

Methods: Two hundred fourteen eyes of 214 patients with DED were analyzed, consisting of 2 groups of patients - 63 with autoimmune dry eye disease (AIDED) and 151 with non-autoimmune dry eye disease (NAIDED). Patients underwent a full clinical examination, including symptom screening, using the Ocular Surface Disease Index (OSDI) questionnaire, and objective analysis of DED signs by Schirmer's testing, tear break-up time (TBUT), Oxford's test, and IVCM corneal imaging.

Clinical characteristics and prognostic factor in juvenile dermatomyositis: data of the Spanish registry.

Background: Juvenile Dermatomyositis (JDM) is the most common chronic idiopathic inflammatory myopathy in children. The diagnosis is clinical. Baseline laboratory and complementary studies trace the phenotype of these patients.

Evaluation of neuroprotective and immunomodulatory properties of mesenchymal stem cells in an ex vivo retinal explant model.

Background: Glaucoma is a blinding degenerative neuropathy in which the death of retinal ganglion cells (RGCs) causes progressive loss of visual field and eventually vision. Neuroinflammation appears to be a key event in the progression and spread of this disease. Thus, microglial immunomodulation represents a promising therapeutic approach in which mesenchymal stem cells (MSCs) might play a crucial role.

Multicenter Study of Secukinumab Survival and Safety in Spondyloarthritis and Psoriatic Arthritis: SEcukinumab in Cantabria and ASTURias Study.

We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting. This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes.

Control of Microbial Opsin Expression in Stem Cell Derived Cones for Improved Outcomes in Cell Therapy.

Human-induced pluripotent stem cell (hiPSC) derived organoids have become increasingly used systems allowing 3D-modeling of human organ development, and disease. They are also a reliable source of cells for transplantation in cell therapy and an excellent model to validate gene therapies. To make full use of these systems, a toolkit of genetic modification techniques is necessary to control their activity in line with the downstream application.

Construct validity of the ASAS health index in psoriatic arthritis: a cross-sectional analysis.

Objectives: The Assessment of SpondyloArthritis international Society health index (ASAS-HI) was designed to assess the global health of patients with spondyloarthritis, but its performance in psoriatic arthritis (PsA) is hardly known. We addressed the clinimetric properties of this instrument in patients with PsA.

Methods: This was a cross-sectional observational study that included 90 consecutive patients with PsA.

AAV-Mediated Gene Delivery to 3D Retinal Organoids Derived from Human Induced Pluripotent Stem Cells.

Human induced pluripotent stem cells (hiPSCs) promise a great number of future applications to investigate retinal development, pathophysiology and cell therapies for retinal degenerative diseases. Specific approaches to genetically modulate hiPSC would be valuable for all of these applications. Vectors based on adeno-associated virus (AAV) have shown the ability for gene delivery to retinal organoids derived from hiPSCs.

IgE Ratio in Tears: A Predictive Tool of Ocular Allergic Inflammation.

Purpose: To demonstrate the tear IgE (measured/exuded) ratio (R) as a useful biological marker of ocular allergy in order to distinguish severe from less severe inflammatory status.

Methods: Tear samples and sera from 78 ocular allergy patients and 19 control subjects were analyzed. Total IgE and albumin were measured for calculating the tear IgE-R defining two subgroups (SG) of samples: R ≥ 4-SG and R < 4-SG.

Relationship Between Chronic Obstructive Pulmonary Disease and Air Pollutants Depending on the Origin and Trajectory of Air Masses in the North of Spain.

Objectives: Chronic obstructive pulmonary disease (COPD) is a common respiratory condition and one of the leading causes of death. Our aim was to analyze the association between emergency room visits due to this disease and meteorological variables and atmospheric contaminant levels in Santander, depending on the origin and trajectory of air masses.

Methods: Data from emergency room visits at Hospital Marqués de Valdecilla were collected on a daily basis during an 8-year period.

Correlation Between the Inflammatory Marker HLA-DR and Signs and Symptoms in Moderate to Severe Dry Eye Disease.

Purpose: To investigate correlations of the inflammatory HLA-DR marker with clinical signs and symptoms commonly used to assess dry eye disease (DED) severity.

Methods: Baseline data were collected from three clinical studies conducted on moderate to severe DED patients. Characteristics of DED were analyzed and correlations were performed in 311 patients.

Effect of benzalkonium chloride on trabecular meshwork cells in a new in vitro 3D trabecular meshwork model for glaucoma.

Purpose: To validate a new culture model of primary human trabecular meshwork cells (p-hTMCs) using Matrigel®, in order to mimic in vitro 3D-TM organization, and to investigate the proinflammatory effect of benzalkonium chloride (BAK) in 3D p-hTMC cultures.

Methods: p-hTMCs, seeded onto Matrigel®-coated inserts were stimulated with BAK (10%), dexamethasone (DEX) (10M) or transforming growth factor-beta 2 (TGF-β2) (5ng/ml) for 48h and observed with confocal microscopy. The BAK effect at 10% or 5.

Thrombocytopenia as a thrombotic risk factor in patients with antiphospholipid antibodies without disease criteria.

Introduction: The antiphospholipid syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis (arterial and/or venous) and/or pregnancy morbidity along with the presence of positive antiphospholipid antibodies (aPL). There is a clear relationship between aPL and some events not included in the clinical criteria, including haematologic.

Objectives: a) to study the probability of developing clinical APS in patients with positive aPL and thrombopenia; b) to identify potential risk factors for thrombosis, and c) to study the association between thrombocytopenia and aPL.

Hyperosmolarity and Benzalkonium Chloride Differently Stimulate Inflammatory Markers in Conjunctiva-Derived Epithelial Cells in vitro.

Tear hyperosmolarity is known to cause ocular surface inflammation in dry eye syndrome. Benzalkonium chloride (BAK), an eyedrop preservative, is known to induce dry eye in long-term-treated patients. Analyzing the modulation of the proinflammatory potential of hyperosmolarity in the presence of BAK on the conjunctiva could give new insights into the effect of this preservative on the disease.

Intraocular pressure reduction and neuroprotection conferred by bone marrow-derived mesenchymal stem cells in an animal model of glaucoma.

Introduction: Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies. Here, we investigated the potential of MSCs therapy in an glaucoma-like ocular hypertension (OHT) model and decipher in vitro the effects of MSCs on primary human trabecular meshwork cells.

Increased extracellular matrix metalloproteinase inducer (EMMPRIN) expression in the conjunctival epithelium exposed to antiglaucoma treatments.

Objective: To analyze the effect of preserved antiglaucoma eye drops on the expression of extracellular matrix (ECM) metalloproteinase inducer (EMMPRIN) in conjunctival epithelial cells.

Methods: A total of 18 patients treated for primary open-angle glaucoma with benzalkonium chloride (BAK) preserved eye drops and eight age-matched controls were included in this study. Glaucoma patients were divided into two groups according to their daily exposure to BAK: high-exposure (HE) group and low-exposure (LE) group.

Effects of benzalkonium chloride on THP-1 differentiated macrophages in vitro.

Purpose: To characterize the effects of benzalkonium chloride (BAK) in THP-1 differentiated cells in vitro.

Methods: Macrophages were obtained after differentiation of THP-1 cells, a human monocytic leukemia cell line. Macrophages were exposed for 24 h to 33 nM (10(-5)%) benzalkonium chloride (BAK), 10 nM dinitrochlorobenzene (DNCB), 100 ng/mL lipopolysaccharide (LPS), 5 ng/mL tumor necrosis factor alpha (TNF-α) or phosphate buffered saline (PBS) as controls.

CX3CL1 expression in the conjunctiva is involved in immune cell trafficking during toxic ocular surface inflammation.

Inappropriate expression of the chemokine CX3CL1 is reportedly known to act on inflammatory conditions in extraocular immune diseases. We studied the expression and effects of CX3CL1 in human patients, cultured human conjunctival cells, and transgenic mice exposed to benzalkonium chloride (BAC), a commonly used preservative in ophthalmic medications despite its proinflammatory properties, to determine whether CX3CL1 is involved in conjunctival inflammation. We report that CX3CL1 expression is increased in the conjunctiva of patients receiving BAC-containing medication, and correlates with clinical inflammation.

Hyperosmolarity potentiates toxic effects of benzalkonium chloride on conjunctival epithelial cells in vitro.

Purpose: Benzalkonium chloride (BAK), the most commonly used preservative in eye drops, is known to induce ocular irritation symptoms and dry eye in long-term treated patients and animal models. As tear film hyperosmolarity is diagnostic of some types of dry eye disease, we determined in vitro on conjunctival epithelial cells the cytoxicity of BAK in hyperosmolar conditions through cell viability, apoptosis, and oxidative stress assays.

Methods: The Wong Kilbourne derivative of Chang conjunctival epithelial cells were cultured for 24 h or 48 h either in NaCl-induced hyperosmolar conditions (400-425-500 mOsM), in low concentrations of BAK (10(-4)%, 3.

Reduced in vivo ocular surface toxicity with polyquad-preserved travoprost versus benzalkonium-preserved travoprost or latanoprost ophthalmic solutions.

The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution(travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride(BAK)-preserved travoprost 0.004% ophthalmic solution(travoprost BAK) and BAK-preserved latanoprost 0.

Conjunctiva-associated lymphoid tissue (CALT) reactions to antiglaucoma prostaglandins with or without BAK-preservative in rabbit acute toxicity study.

Conjunctiva-associated lymphoid tissue (CALT) is closely associated with ocular surface immunity. This study investigated the effects of antiglaucoma prostaglandin analogs with or without benzalkonium chloride (BAK) preservative on organized CALT using an acute toxic model. A total of 48 albino rabbits were used and seven groups of treatments were constituted.

In vitro interactions between peripheral blood lymphocytes and the Wong-Kilbourne derivative of Chang conjunctival cells.

Purpose: To investigate the interactions between conjunctival cells and peripheral blood lymphocytes (PBLs) in vitro and to analyze the role of benzalkonium chloride (BAC)-induced apoptosis in this model.

Methods: Wong-Kilbourne derivative (WKD) cells were cocultured in cell-contact cultures or on cell inserts for 1 to 7 days with PBLs, activated or not with phorbol 12-myristate 13-acetate (PMA). Morphologic analyses of cell interactions were performed using membrane stainings (green PKH67 for WKD cells and red PKH26 for PBL), F-actin immunostaining, and scanning electron microscopy.

Comparative in vitro toxicology study of travoprost polyquad-preserved, travoprost BAK-preserved, and latanoprost BAK-preserved ophthalmic solutions on human conjunctival epithelial cells.

Purpose: To compare the toxicological profile of a new formulation of travoprost 0.004% ophthalmic solution (travoprost PQ), containing the preservative polyquaternium-1(PQ, polyquad), with the commercially available formulation of benzalkonium chloride (BAK)-preserved travoprost 0.004% ophthalmic solution (travoprost BAK) and BAK-preserved latanoprost 0.

Multiple endpoint analysis of BAC-preserved and unpreserved antiallergic eye drops on a 3D-reconstituted corneal epithelial model.

Purpose: To compare the effects of benzalkonium chloride (BAC)-preserved and unpreserved antiallergic eye drops on the human 3D-reconstituted corneal epithelial model (3D-HCE).

Methods: 3D-HCE were treated for 24 h followed or not by a 24 h post-incubation recovery period (24 h+24 h) with phosphate-buffered saline (PBS), 0.01% BAC, unpreserved formulations of ketotifen, N Acetyl-Aspartyl Glutamic Acid (NAAGA), cromoglycate, or BAC-preserved commercial formulations of ketotifen, olopatadine, epinastine, and levocabastine.

Toxicological evaluation of preservative-containing and preservative-free topical prostaglandin analogues on a three-dimensional-reconstituted corneal epithelium system.

Aims: Using an established three-dimensional (3D) toxicological model based on reconstituted human corneal epithelium (HCE), this study investigated the tolerability of four topical intraocular-pressure-lowering agents: the commercial solutions of benzalkonium chloride (BAC)-containing 0.005% latanoprost, 0.004% travoprost, 0.

Polyquad-preserved travoprost/timolol, benzalkonium chloride (BAK)-preserved travoprost/timolol, and latanoprost/timolol in fixed combinations: a rabbit ocular surface study.

Introduction: The aim of this study was to use a validated acute rabbit model to test the toxicity of a novel formulation of fixed-combination travoprost 0.004%/timolol 0.5% ophthalmic solution, which contains the antimicrobial preservative polyquaternium-1 (PQ), compared with the commercial formulation of fixed combinations travoprost 0.