TFOS Lifestyle: Impact of cosmetics on the ocular surface.

In this report the use of eye cosmetic products and procedures and how this represents a lifestyle challenge that may exacerbate or promote the development of ocular surface and adnexal disease is discussed. Multiple aspects of eye cosmetics are addressed, including their history and market value, psychological and social impacts, possible problems associated with cosmetic ingredients, products, and procedures, and regulations for eye cosmetic use. In addition, a systematic review that critically appraises randomized controlled trial evidence concerning the ocular effects of eyelash growth products is included.

Heterochronic Parabiosis Causes Dacryoadenitis in Young Lacrimal Glands.

Aging is associated with inflammation and oxidative stress in the lacrimal gland (LG). We investigated if heterochronic parabiosis of mice could modulate age-related LG alterations. In both males and females, there were significant increases in total immune infiltration in isochronic aged LGs compared to that in isochronic young LGs.

Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism.

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome.

OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2.

Purpose: We evaluate the treatment effect of OC-01 (varenicline solution) nasal spray (VNS) in dry eye disease (DED) subjects from two randomized trials who self-reported autoimmune disease (AID).

Patients And Methods: Post hoc subgroup analysis of subjects reporting a history of AID from the integrated OC-01 VNS 0.03 or 0.

Ectopic lymphoid structures in the aged lacrimal glands.

Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated.

Effects of Long-Term Wear and Discontinuation of Orthokeratology Lenses on the Eyeball Parameters in Children with Myopia.

To evaluate the effects of long-term wear and discontinuation of the orthokeratology lenses (Orth-K) on the biological parameters of eyeballs in children with myopia. In this prospective study, a total of 308 subjects with myopia were randomized to receive Orth-K (n = 154) or single vision spectacles (SVS) (n = 154) for 12 months followed by a 1-month withdrawal period. The axial length (AL), the central corneal thickness (CCT), the anterior chamber depth (ACD) and the central lens thickness (CLT) were assessed at the baseline, 6 months, 12 months, and 13 months (1-month after lens withdrawal).

Molecular mechanisms regulating wound repair: Evidence for paracrine signaling from corneal epithelial cells to fibroblasts and immune cells following transient epithelial cell treatment with Mitomycin C.

In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair. We use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elevated levels of immunomodulatory proteins including IL-1α and TGFβ1 compared to cells exposed to CMC. These factors increase epithelial and macrophage phagocytosis and promote ECM turnover.

A, B, C's of Trk Receptors and Their Ligands in Ocular Repair.

Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis.

Spatial transcriptomics of the lacrimal gland features macrophage activity and epithelium metabolism as key alterations during chronic inflammation.

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren's syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.

Imbalanced IL-37/TNF-α/CTSS signaling disrupts corneal epithelial barrier in a dry eye model in vitro.

Purpose: To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease.

Methods: Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2-48 h).

New, potent, small molecule agonists of tyrosine kinase receptors attenuate dry eye disease.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this.

Mucosal immunology of the ocular surface.

The eye is a sensory organ exposed to the environment and protected by a mucosal tissue barrier. While it shares a number of features with other mucosal tissues, the ocular mucosal system, composed of the conjunctiva, Meibomian glands, and lacrimal glands, is specialized to address the unique needs of (a) lubrication and (b) host defense of the ocular surface. Not surprisingly, most challenges, physical and immunological, to the homeostasis of the eye fall into those two categories.

Establishment of a bi-layered tissue engineered conjunctiva using a 3D-printed melt electrowritten poly-(ε-caprolactone) scaffold.

Purpose: To utilize melt electrowriting (MEW) technology using poly-(ε-caprolactone) (PCL) coupled with a 2-step co-culturing strategy for the development of a conjunctival bi-layer synthetic construct.

Methods: Melt electrowritten scaffolds using PCL were fabricated using an in-house-built MEW printer. Human conjunctival stromal cells (CjSCs) and epithelial cells (CjECs) were isolated from donor tissue.

Adverse Effects and Safety in Glaucoma Patients: Agreement on Clinical Trial Outcomes for Reports on Eye Drops (ASGARD)-A Delphi Consensus Statement.

Purpose: The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops.

Design: Modified Delphi method.

Methods: Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in 2 sequential web-based surveys administered from June 27 to August 29, 2021.

Management Strategies for Evaporative Dry Eye Disease and Future Perspective.

Dry eye disease (DED) is a common disorder that remains challenging from a clinical perspective. Unstable or deficient tear film is a major factor contributing to DED and the inability to resolve the loss of tear film homeostasis that accompanies DED can result in a vicious circle of inflammation and treatment-refractory disease. Recently recognized as a multifactorial disease, the main etiological subtypes of DED are aqueous-deficient and evaporative which exist on a continuum, although evaporative dry eye (EDE) is the more frequent classification.

IL-17 Producing Lymphocytes Cause Dry Eye and Corneal Disease With Aging in RXRα Mutant Mouse.

Purpose: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.

Methods: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells.

Gut Microbiota From Sjögren syndrome Patients Causes Decreased T Regulatory Cells in the Lymphoid Organs and Desiccation-Induced Corneal Barrier Disruption in Mice.

Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy ( = 20), dry eye ( = 4) and SS ( = 7) subjects.

Gut-derived butyrate suppresses ocular surface inflammation.

Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface.

Immune phenotype of the CD4 T cells in the aged lymphoid organs and lacrimal glands.

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4 T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4CD25GITR) and non-Tregs (CD4CD25GITR) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel.

IL-36α/IL-36RA/IL-38 signaling mediates inflammation and barrier disruption in human corneal epithelial cells under hyperosmotic stress.

Purpose: To explore the distinct expression and diverse roles of IL-36 cytokines in dry eye disease using an in vitro hyperosmolarity model of human corneal epithelial cells (HCECs).

Methods: Primary HCECs were cultured from fresh donor limbal explants. Hyperosmolarity model was established by switching HCECs from isosmotic (312 mOsM) to hyperosmotic medium (350-500 mOsM) alone or with addition of rhIL-36RA or rhIL-38 for 2-48 h.

Successful management of chronic Blepharo-rosacea associated demodex by lid scrub with terpinen-4-ol.

Purpose: To report a successful treatment of chronic rosacea associated ocular demodicosis with lid scrub containing terpinen-4-ol (T4O).

Observations: A 72-year old woman presented with recurrent and refractory ocular erythema, irritation, dryness, and photophobia despite conventional medical treatment (artificial tears, hypochlorous acid lid hygiene, doxycycline, and erythromycin) for 5 years. Examination revealed facial erythema, telangiectasias on cheeks, nose and lids, and cylindrical dandruff (CD) on bilateral upper and lower lashes.

Safety and feasibility of subconjunctival injection of mesenchymal stem cells for acute severe ocular burns: A single-arm study.

Purpose: To investigate the safety and feasibility of topical injection of bone marrow derived mesenchymal stem cells (BM-MSCs) in acute severe ocular burns.

Methods: In this open-label，single-arm study, subconjunctival injection of allogenic BM-MSCs combined with standard treatment was given to 16 patients with acute severe ocular burns (Dua's grade IV to VI) within 2 weeks after injury. The primary outcome was efficacy rate which referred to the proportion of complete corneal epithelialization patients without perforation.

Tissue engineering of corneal stroma via melt electrowriting.

The cornea serves as the main refractive component of the eye with the corneal stroma constituting the thickest component in a stratified layered system of epithelia, stroma, and endothelium. Current treatment options for patients suffering from corneal diseases are limited to transplantation of a human donor cornea (keratoplasty) or to implantation of an artificial cornea (keratoprosthesis). Nevertheless, donor shortage and failure of artificial corneas to integrate with local tissue constitute important problems that have not been yet circumvented.