How does ocular graft-versus-host disease fit under the dry eye umbrella? A review.

Graft-versus-host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments.

Lipids from ocular meibum and tears may serve as biomarkers for depression and post-traumatic stress disorder.

BACKGROUND: There is a need to develop biomarkers for diagnosis and prediction of treatment responses in depression and post-traumatic stress disorder (PTSD). METHODS: Cross-sectional study examining correlations between tear inflammatory proteins, meibum and tear sphingolipids, and symptoms of depression and PTSD-associated anxiety. Ninety individuals filled depression (Patient Health Questionnaire 9, PHQ-9) and PTSD-associated anxiety (PTSD Checklist-Military Version, PCL-M) questionnaires. In 40 patients, a multiplex assay system was used to quantify 23 inflammatory proteins in tears. In a separate group of 50 individuals, liquid chromatography-mass spectrometry was performed on meibum and tears to quantify 34 species of sphingolipids, encompassing ceramides, monohexosyl ceramides and sphingomyelins. RESULTS: The mean age of the population was 59.4 ± 11.0 years; 89.0% self-identified as male, 34.4% as White, 64.4% as Black, and 16.7% as Hispanic. The mean PHQ-9 score was 11.1 ± 7.6, and the mean PCL-M score was 44.3 ± 19.1. Symptoms of depression and PTSD-associated anxiety were highly correlated (ρ =0.75, p < 0.001). Both PHQ9 and PCL-M scores negatively correlated with multiple sphingolipid species in meibum and tears. In multivariable models, meibum Monohexosyl Ceramide 26:0 (pmol), tear Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 16:0 (mol%), and tear Ceramide 26:1 (mol%) remained associated with depression and meibum Monohexosyl Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 26:0 (pmol), tear Sphingomyelin 20:0 (mol%), and tear Sphingosine-1-Phosphate (mol%) remained associated with PTSD-associated anxiety. CONCLUSIONS: Certain meibum and tear sphingolipid species were related to mental health indices. These interactions present opportunities for innovative diagnostic and therapeutic approaches for mental health disorders.

Automated identification and quantification of activated dendritic cells in central cornea using artificial intelligence.

PURPOSE: To validate an algorithm quantifying activated dendritic cells (aDCs) using in-vivo confocal microscopy (IVCM) images. METHODS: IVCM images obtained at the Miami Veterans Affairs Hospital were retrospectively analyzed. ADCs were quantified both with an automated algorithm and manually. Intra-class-correlation (ICC) and a Bland-Altman plot were used to compare automated and manual counts. As a secondary analysis, individuals were grouped by Dry Eye (DE) subtype: 1) aqueous-tear deficiency (ATD; Schirmer's test ≤5 mm); 2) evaporative DE (EDE; TBUT≤5s); or 3) control (Schirmer's test>5 mm; TBUT>5s) and ICCs were re-examined. RESULTS: 173 non-overlapping images from 86 individuals were included in this study. The mean age was 55.2 ± 16.7 years; 77.9% were male; 20 had ATD; 18 EDE and 37 were controls. The mean number of aDCs in the central cornea quantified automatically was 0.83 ± 1.33 cells/image and manually was 1.03 ± 1.65 cells/image. A total of 143 aDCs were identified by the automated algorithm and 178 aDCs were identified manually. While a Bland-Altman plot indicated a small difference between the two methods (0.19, p < 0.01), the ICC of 0.80 (p = 0.01) demonstrated excellent agreement. Secondarily, similar results were found by DE type with an ICC of 0.75 (p = 0.01) for the ATD group, 0.80 (p = 0.01) for EDE, and 0.82 (p = 0.01) for controls. CONCLUSIONS: Quantification of aDCs within the central cornea may be successfully estimated using an automated machine learning based algorithm. While this study suggests that analysis using artificial intelligence has comparable results with manual quantification, further longitudinal research to validate our findings in more diverse populations may be warranted.

Living with Dry Eye Disease and its Effects on Quality of Life: Patient, Optometrist, and Ophthalmologist Perspectives.

Dry eye disease is a very common condition, especially among aging women. People often think of it as a very mild and non-harmful issue, but the reality is that it has a huge deleterious effect on patients' quality of life. Most publications usually focus on the scientific aspects of this pathology: its epidemiology, diagnosis, or management. However, in this article we highlight the patient's perspective and the challenges of living with dry eye disease. With prior informed consent, we interviewed a patient whose life has drastically changed since she first got the diagnosis. We also asked healthcare professionals based in Miami who were involved in this patient's care for their opinions. We hope that the messages and commentaries resonate with patients and physicians involved in the care of dry eye disease worldwide.

A multicenter report of the use of plasma rich in growth factors (PRGF) for the treatment of patients with ocular surface diseases in North America.

PURPOSE: To investigate the efficacy and safety of plasma rich in growth factors (PRGF) eyedrops in the management of patients with ocular surface diseases in North America. METHODS: Multicenter interventional case series of patients using PRGF eyedrops for the first time. A cohort of patients was analyzed for corneal staining score at initial visit and at 3 months of therapy with PRGF. Another cohort responded to a 10-item questionnaire that evaluated patients' satisfaction and safety, which included the symptom assessment questionnaire in dry eye (SANDE) score, after 6 months of PRGF treatment. RESULTS: A total of 153 patients were analyzed. Of these, 102 were reviewed for corneal epitheliopathy and 99 patients responded to the questionnaire. The mean (±SD) age of the population was 63.7 ± 17 years and 72.5% were female. The clinical indications for PRGF usage were dry eye (60%), neurotrophic keratopathy (15%), dormant corneal ulcers (12%), limbal stem cell deficiency (10%), and cicatrizing conjunctivitis (4%). At the final visit, 74.3% of patients showed an improvement of their corneal staining. Those who had punctate epithelial erosions or epithelial defects were reduced from 76.5% to 47% and 23.5% to 7.8% respectively (p < 0.0001). Symptoms, measured via SANDE score, significantly decreased from a median of 90 to 34.6 out of 100 points on follow-up (p < 0.0001). Only one patient (0.98%) complained of ocular burning sensation as a side effect. CONCLUSIONS: This multicentric study demonstrates the safety and efficacy of the use of PRGF for treating signs and symptoms in patients with significant ocular surface diseases.

Role of Caspase-1 as a Biomarker of Ocular Surface Damage.

PURPOSE: To examine the potential of caspase-1 as a biomarker for ocular surface damage. DESIGN: Cross-sectional study. METHODS: A total of 113 tear samples (64 subjects) were analyzed. Sixty-one samples were from individuals with dry eye disease (DED), defined as Ocular Surface Disease Index (OSDI) ≥13 and/or corneal staining (CS) ≥3; 32 were from individuals who used glaucoma medication, irrespective of DED metrics; and 20 were from controls (CS <3 and OSDI <13). All individuals completed a medical history form and underwent an ocular surface assessment. Protein levels of caspase-1 were determined by enzyme-linked immunosorbent assay off Schirmer's strips. The primary analysis compared caspase-1 levels in individuals with signs of ocular surface damage (CS ≥3) in both case groups and controls. Secondary correlational analyses were conducted to examine relationships between caspase-1 levels and ocular signs and symptoms. Finally, area under the curve (AUC) analyses were performed to examine relationships between inflammatory markers and CS. RESULTS: The mean age of the population was 58±18 years; 70% were female. Tear samples from individuals with ocular surface damage presented higher caspase-1 levels than the control group. Caspase-1 levels showed a moderate positive correlation with CS (Spearman r = 0.31; P = .001) and eye redness (Spearman r = 0.39; P = .004), and a negative correlation with Schirmer's (Spearman r = -0.46; P < .001) and tear break-up time (Spearman r = -0.33; P = .0006). Caspase-1 showed higher sensitivity and AUC for detecting ocular surface damage than InflammaDry, and its expression was not affected by anti-inflammatory agents. CONCLUSION: Caspase-1 levels were higher in the tears of individuals with ocular surface damage, suggesting its potential to be used as a biomarker and/or therapeutic target.

Tumor necrosis factor-alpha and interferon-gamma induce inflammasome-mediated corneal endothelial cell death.

PURPOSE: Chronic corneal endothelial cell (CEC) loss results in corneal edema and vision loss in conditions such as pseudophakic bullous keratopathy (PBK), Fuchs' dystrophy, and corneal graft failure. Low CEC density has been associated with an elevation of intraocular pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (INF)-γ. These cytokines are capable of triggering pyroptosis, a programmed cell death mechanism mediated by the inflammasome, prompting the activation of the pro-inflammatory cytokine interleukin (IL)-1ß, the perpetuation of inflammation, and subsequent damage of corneal endothelial tissue. Therefore, the purpose of this study was to determine the deleterious contribution of the inflammasome and pyroptosis to CEC loss. METHODS: CECs from human donor corneas were treated ex vivo with TNF-α and IFN-γ for 48 h. Levels of caspase-1 and IL-1ß were then assayed by ELISA, and the expression of caspase-1 and gasdermin-D (GSDM-D) were confirmed by immunofluorescence. Endothelial cell damage was analyzed by a lactate dehydrogenase (LDH) release assay, and oxidative stress was determined by measuring the levels of reactive oxygen species (ROS) in the culture media. RESULTS: Inflammasome activation and oxidative stress were elevated in CECs following exposure to TNF-α and IFN-γ, which resulted in cell death by pyroptosis as determined by LDH release which was inhibited by the caspase-1 inhibitor Ac-YVAD-cmk. CONCLUSION: CEC death is induced by the pro-inflammatory cytokines TNF-α and IFN-γ, which contribute to inflammasome activation. Moreover, the inflammasome is a promising therapeutic target for the treatment of chronic CEC loss.

Use of Acellular Umbilical Cord-Derived Tissues in Corneal and Ocular Surface Diseases.

Blood derived products have become a valuable source of tissue for the treatment of ocular surface diseases that are refractory to conventional treatments. These can be obtained from autologous or allogeneic sources (patient's own blood or from healthy adult donors/umbilical cord blood, respectively). Allogeneic cord blood demonstrates practical advantages over alternatives and these advantages will be discussed herein. Umbilical cord blood (UCB) can be divided, generally speaking, into two distinct products: first, mononuclear cells, which can be used in regenerative ophthalmology, and second, the plasma/serum (an acellular fraction), which may be used in the form of eyedrops administered directly to the damaged ocular surface. The rationale for using umbilical cord serum (UCS) to treat ocular surface diseases such as severe dry eye syndrome (DES), persistent epithelial defects (PED), recurrent epithelial erosions, ocular chemical burns, graft versus host disease (GVHD), among others, is the considerably high concentration of growth factors and cytokines, mimicking the natural healing properties of human tears. Allogeneic serum also offers the opportunity for therapeutic treatment to patients who, due to poor heath, cannot provide autologous serum. The mechanism of action involves the stimulation of endogenous cellular proliferation, differentiation and maturation, which is highly efficient in promoting and enhancing corneal epithelial healing where other therapies have previously failed.

Contaminación enteroparasitaria de moscas capturadas en el municipio Palavecino, estado Lara, Venezuela, 2017 / Enteroparasitary contamination of flies captured in the Palavecino Municipality, Lara State, Venezuela, 2017

Introducción: la falta de estudios en Venezuela que demostraran la importancia de moscas de interés médico como vectores mecánicos de enteroparásitos, motivó la realización de este trabajo descriptivo transversal, con muestra intencional, donde con trampas plásticas y ecológicas se capturaron adultos de moscas. Materiales y método: los ejemplares eran inactivados, para luego ser clasificadas por género, lavados con solución salina 0,85%, separados de la solución, y luego esta era centrifugada 10 minutos a 3.000 rpm, para posteriormente utilizar el pelet, el cual se montaba entre lámina y laminilla para observar el sedimento al microscopio. Resultados: se lograron capturar 1.061 adultos de moscas, los cuales correspondían taxonómicamente a los géneros: Phaenicia sp (29,2%), Blepharicnema splendens (6,4%), Cochliomyia hominivorax (3,8%), Musca domestica (3,4%), Sarcophaga sp; (3%), Cochliomyia macellaria (2,5%) y la sumatoria de otras especies (51,7%), tal que, de más de siete especies de moscas, se logró identificar los enteroparásitos Blastocystis sp, Endolimax nana, Entamoeba hartmanni, Entamoeba histolytica/dispar, Entamoeba coli, Iodamoeba butschlii, Pentatrichomonas sp (Trichomonas sp), mientras que los únicos helmintos conseguidos fueron las uncinarias (Anquilostomideos). Conclusiones: la contaminación enteroparasitaria de más de siete especies de moscas, con siete especies de enteroparásitos diagnosticados, resalta el papel transmisor de estos dípteros en el ciclo de los parásitos entéricos. (AU)

Introduction: the lack of studies in Venezuela that demonstrate the importance of flies of medical interest as mechanical vectors of enteroparasites, motivated the realization of this crosssectional descriptive work, with intentional sample, where with plastic and ecological traps, adults of flies were captured. Materials and methods: the specimens were inactivated, to be classified by gender, washed with 0.85% saline, separated from the solution and then centrifuged 10 min at 3000 rpm, to later use the pellet, which was mounted between lamina and lamella to observe the sediment under a microscope. Results: 1.061 adults of flies were captured, which corresponded taxonomically to the genera: Phaenicia sp (29,2%), Blepharicnema splendens (6,4%), Cochliomyia hominivorax (3,8%), Musca domestica (3,4), Sarcophaga sp; (3%), Cochliomyia macellaria (2,5%) and the sum of other species (51,7%), such that from more than seven species of flies were able to identify the enteroparasites: Blastocystis sp, Endolimax nana, Entamoeba hartmanni , Entamoeba histolytica/dispar, Entamoeba coli, Iodamoeba butschlii, Pentatrichomonas sp (Trichomonas sp), while the only helminths obtained were Uncinarias (Anquilostomideos). Conclusions: the enteroparasitic contamination of more than seven species of flies with seven species of enteroparasites diagnosed highlights the role of these dipterous transmitters in the cycle of enteric parasites.

Introdução: a falta de estudos demonstrando Venezuela voa a importância de interesse médico como vetores mecânicos enteroparasitas, conduziu à realização do presente trabalho descritiva em corte transversal, onde amostra intencional com plástico e armadilhas ecológicas, moscas adultas foram capturados. Materiais e métodos: as amostras foram inactivadas, e, em seguida, são classificados por género, lavada com 0,85% de solução salina, separado da solução e, em seguida, esta foi centrifugado 10 min a 3000 rpm, e, em seguida, usando o sedimento, que foi montado entre a lâmina e a lamela para observar o sedimento ao microscópio. Resultados: conseguiram capturar 1.061 moscas adultas, que taxonomicamente correspondiam aos géneros: Phaenicia sp (29,2%), Blepharicnemasplendens (6,4%), Cochliomyia hominivorax (3,8%), Musca domestica (3,4), Sarcophaga sp; (3%), Cochliomyia macellaria (2,5%) e a soma de outras espécies (51,7%), de modo que mais do que sete espécies de moscas podem ser identificados parasitas intestinais: Blastocystis sp, Endolimax nana, Entamoeba hartmanni histolytica / dispar Entamoeba, Entamoeba coli, Iodamoeba butschlii, Pentatrichomonas sp (Trichomonas sp), ao passo que apenas foram obtidos helmintos Uncinarias (Ancilóstomo). Conclusões: contaminação enteroparasitaria de mais de sete espécies de moscas com sete espécies de parasitas intestinais sublinha o papel destes transmissor Diptera no ciclo de parasitas entéricos diagnosticados.