Inflammation in Dry Eye Disease-Pathogenesis, Preclinical Animal Models, and Treatments.

Dry eye disease (DED) is a rapidly growing ocular surface disease with a significant socioeconomic impact that affects the patients' visual function and, thus, their quality of life. It is distinguished by a loss of tear film homeostasis, leading to tear film instability, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities, with all of these playing etiological roles in the propagation of the vicious DED circle. While current treatments primarily focus on reducing tear film instability and hyperosmolarity, increasingly more attention is being placed on tackling the underlying inflammation that propagates and potentiates these factors.

Objective Analysis of Corneal Nerves and Dendritic Cells.

Corneal nerves and dendritic cells are increasingly being visualised to serve as clinical parameters in the diagnosis of ocular surface diseases using intravital confocal microscopy. In this review, different methods of image analysis are presented. The use of deep learning algorithms, which enable automated pattern recognition, is explained in detail using our own developments and compared with other established methods.

Immunologic basis for development of keratoconjunctivitis sicca in systemic autoimmune diseases: Role of innate immune sensors.

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve.

Murine models of graft versus host disease (GVHD): Focus on ocular GVHD.

Graft versus host disease (GVHD) remains a major and serious complication of allogeneic hematopoietic stem cell transplantation. Based on the time of onset, clinical phenotypes, progression kinetics, and pathophysiology, GVHD is stratified into acute, chronic, and overlapping types. The eyes are among the most commonly affected organs in GVHD.

[Differential diagnoses of ocular mucous membrane pemphigoid].

Overall, conjunctival scarring is rare and often overlooked during routine examination. However, the differential diagnostic distinction of cicatricial mucous membrane pemphigoid from other causes is crucial for further treatment planning. Other entities that lead to conjunctival scarring, are ocular rosacea, ocular graft-versus-host disease, atopic keratoconjunctivitis, infections, trauma and further sometimes very rare diseases.

A Novel Ferroptosis Inhibitor UAMC-3203, a Potential Treatment for Corneal Epithelial Wound.

Corneal wound, associated with pain, impaired vision, and even blindness, is the most common ocular injury. In this study, we investigated the effect of a novel ferroptosis inhibitor, UAMC-3203 (10 nM-50 µM), in corneal epithelial wound healing in vitro in human corneal epithelial (HCE) cells and ex vivo using alkali-induced corneal wounded mice eye model. We evaluated in vivo acute tolerability of the compound by visual inspection, optical coherence tomography (OCT), and stereomicroscope imaging in rats after its application (100 µM drug solution in phosphate buffer pH 7.

Olive Pomace Phenolic Compounds: From an Agro-Industrial By-Product to a Promising Ocular Surface Protection for Dry Eye Disease.

Dry eye (DED) is a prevalent disease with immune-mediated inflammation as the principal pathophysiological etiology. Olive pomace, the major by-product of the olive oil industry, is rich in high-value polyphenols. Their anti-inflammatory and immunomodulatory activities were determined on human CD4+ T cells (hTCD4+) and in a DED animal model.

Desiccating Stress Significantly Increases the Risk for Chronic Ocular Graft-versus-Host-Disease.

Desiccating stress (DS) is known to induce dry eye disease but has not been studied in the context of ocular graft-versus-host disease (oGVHD). Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are exposed to DS on transplantation wards, which are highly climate-regulated for hygienic purposes. Because oGVHD demonstrates features of dry eye disease, this retrospective study aimed to analyze DS as a risk factor for chronic oGVHD.

Segmentation and Evaluation of Corneal Nerves and Dendritic Cells From In Vivo Confocal Microscopy Images Using Deep Learning.

Purpose: Segmentation and evaluation of in vivo confocal microscopy (IVCM) images requires manual intervention, which is time consuming, laborious, and non-reproducible. The aim of this research was to develop and validate deep learning-based methods that could automatically segment and evaluate corneal nerve fibers (CNFs) and dendritic cells (DCs) in IVCM images, thereby reducing processing time to analyze larger volumes of clinical images.

Methods: CNF and DC segmentation models were developed based on U-Net and Mask R-CNN architectures, respectively; 10-fold cross-validation was used to evaluate both models.

Dynamic Contrast Microscopic Optical Coherence Tomography As a Novel Method for Assessing Corneal Epithelium During Exposure to Benzalkonium Chloride.

Purpose: Microscopic optical coherence tomography (mOCT) has an imaging resolution of 1 µm in all voxel dimensions, but individual epithelial cells are difficult to resolve due to lack of scattering contrast. Adding dynamic contrast processing to mOCT (dmOCT) results in color images that enable visualization of individual cells and possibly give information on cellular function via the calculation of a motility coefficient. We propose this technique as a novel method of evaluating the ocular surface after exposure to a toxic chemical, benzalkonium chloride (BAK).

Outcomes and complications of cataract surgery in patients with chronic ocular graft-versus-host-disease-a multicenter, retrospective analysis.

Purpose: To evaluate the outcome of phacoemulsification in patients with chronic ocular Graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (aHSCT).

Methods: Retrospective, observational multicenter study from 1507 oGVHD patients. From the patient files, data were collected including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Schirmer's test I, tear film break-up time (TFBUT), corneal fluorescein staining score, postoperative complications, and pre- and post-operative topical therapy.

Topical application of cannabinoid-ligands ameliorates experimental dry-eye disease.

Purpose: Dry eye disease (DED) is a multifactorial disease, with limitations regarding efficacy and tolerability of applied substances. Among several candidates, the endocannabinoid system with its receptors (CB1R and CB2R) were reported to modulate inflammation, wound healing and pain, which are also core DED pathomechanisms. This study is to investigate the therapeutic responses of Δ-9 tetrahydrocannabinol (a non-selective agonist) and two selective antagonists, SR141716A (CB1R antagonist) and SR144528 (CB2R antagonist), as a topical application using a DED mouse model.

Ocular Graft-versus-Host Disease in a Chemotherapy-Based Minor-Mismatch Mouse Model Features Corneal (Lymph-) Angiogenesis.

Ocular graft-versus-host disease (oGVHD) is a fast progressing, autoimmunological disease following hematopoietic stem cell transplantation, leading to severe inflammation of the eye and destruction of the lacrimal functional unit with consecutive sight-threatening consequences. The therapeutic "window of opportunity" is narrow, and current treatment options are limited and often insufficient. To achieve new insights into the pathogenesis and to develop new therapeutic approaches, clinically relevant models of oGVHD are desirable.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIa. The 2020 Clinical Implementation and Early Diagnosis Working Group Report.

Recognition of the earliest signs and symptoms of chronic graft-versus-host disease (GVHD) that lead to severe manifestations remains a challenge. The standardization provided by the National Institutes of Health (NIH) 2005 and 2014 consensus projects has helped improve diagnostic accuracy and severity scoring for clinical trials, but utilization of these tools in routine clinical practice is variable. Additionally, when patients meet the NIH diagnostic criteria, many already have significant morbidity and possibly irreversible organ damage.

Deep learning-based automatic meibomian gland segmentation and morphology assessment in infrared meibography.

Meibomian glands (MG) are large sebaceous glands located below the tarsal conjunctiva and the abnormalities of these glands cause Meibomian gland dysfunction (MGD) which is responsible for evaporative dry eye disease (DED). Accurate MG segmentation is a key prerequisite for automated imaging based MGD related DED diagnosis. However, Automatic MG segmentation in infrared meibography is a challenging task due to image artifacts.

Meibomian Gland Dysfunction in Ocular Graft vs. Host Disease: A Need for Pre-Clinical Models and Deeper Insights.

Despite decades of experience with hematopoietic stem cell transplantation, we are still faced with the delicate equipoise of achieving stable ocular health post-transplantation. This is because ocular graft-versus-host disease (oGvHD) following hematopoietic stem cell transplantation frequently occurs (≥50%) among transplant patients. To date, our understanding of the pathophysiology of oGvHD especially the involvement of the meibomian gland is still limited as a result of a lack of suitable preclinical models among other.

Clinical Dry Eye and Meibomian Gland Features Among Dry Eye Patients in Rural and Urban Ghana.

Aim: To compare differences in clinical dry eye features and meibomian gland health status between dry eye patients from rural and urban populations in Ghana.

Methods: We examined 211 (rural=109, urban=102) participants with subjective dry eye symptoms. Tear film break -up time (TBUT), Schirmer's test and ocular surface staining (OSS) were assessed.

Obese Mice with Dyslipidemia Exhibit Meibomian Gland Hypertrophy and Alterations in Meibum Composition and Aqueous Tear Production.

Background: Dyslipidemia may be linked to meibomian gland dysfunction (MGD) and altered meibum lipid composition. The purpose was to determine if plasma and meibum cholesteryl esters (CE), triglycerides (TG), ceramides (Cer) and sphingomyelins (SM) change in a mouse model of diet-induced obesity where mice develop dyslipidemia.

Methods: Male C57/BL6 mice (8/group, age = 6 wks) were fed a normal (ND; 15% kcal fat) or an obesogenic high-fat diet (HFD; 42% kcal fat) for 10 wks.

Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy.

Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse models of dry-eye disease and ocular allergy.

Detection of systemic immunosuppressants in autologous serum eye drops (ASED) in patients with severe chronic ocular graft versus host disease.

Purpose: Chronic graft versus host disease is a major consequence after allogeneic stem cell transplantation (allo-SCT) and has great impact on patients' morbidity and mortality. Besides the skin, liver, and intestines, the eyes are most commonly affected, manifesting as severe ocular surface disease. Treatment protocols include topical steroids, cyclosporine, tacrolimus, and ASED.

Tolerance and Adherence to Cationic 0.1% Cyclosporine in Ocular Graft-versus-Host Disease.

Introduction: Anti-inflammatory, topical therapy of severe keratitis in dry eye disease (DED) and ocular graft-versus-host disease (oGvHD) includes steroids, cyclosporine (Cs), and others. In Germany, a commercial product containing 0.1% Cs in a cationic formulation is available since 2015.