Enhancing Ocular Surface in Dry Eye Disease Patients: A Clinical Evaluation of a Topical Formulation Containing Sesquiterpene Lactone Helenalin.

The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 (p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores (p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer's test scores (p < 0.001), whereas Group 2 did not (p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.

Prevalence and clinical characteristics of neurotrophic keratopathy in hispanic population in northeastern Mexico.

PURPOSE: To evaluate the prevalence and clinical characteristics of neurotrophic keratopathy (NK) in northeastern Mexico. METHODS: Retrospective cross-sectional study in which NK patients admitted to our ophthalmology clinic between 2015 and 2021 were consecutively enrolled. Data regarding demographics, clinical characteristics, and comorbidities were collected at the time diagnosis of NK was made. RESULTS: In the period from 2015 to 2021, a total of 74,056 patients were treated and of these 42 had a diagnosis of neurotrophic keratitis. The prevalence found was 5.67 [CI95 3.95-7.38] in 10,000 cases. The mean age observed was 59 ± 17.21 years occurring more frequently in males in 59% and with corneal epithelial defects in 66.7%. The most frequent antecedents were the use of topical medications in 90%, the presence of diabetes mellitus 2 in 40.5% and systemic arterial hypertension in 26.2%. A higher proportion of male patients with corneal alterations and a higher proportion of female patients with corneal ulcerations and/or perforation were observed. CONCLUSION: Neurotrophic keratitis is an underdiagnosed disease with a broad clinical spectrum. The antecedents that were contracted corroborate what was reported in the literature as risk factors. The prevalence of the disease in this geographical area was not reported, so it is expected to increase over time when searching for it intentionally.

An Oral Polyphenol Formulation to Modulate the Ocular Surface Inflammatory Process and to Improve the Symptomatology Associated with Dry Eye Disease.

Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life. Thus, they show poor bioavailability. To overcome these limitations and improve their stability and bioavailability, we evaluated the safety and efficacy of an oral formulation containing among other compounds, polyphenols and omega-3 fatty acids, with the addition of a surfactant in patients with DED. Subjects were randomly assigned to one of four study groups including the study formulation (A), placebo (P), the study formulation + eye lubricant (A + L), and placebo + eye lubricant (P + L). Patients from the A and P groups were instructed to take two capsules every 24 h, while patients in the L groups also added one drop of lubricant twice a day for 12 weeks as well. Regarding safety, non-ocular abnormalities were observed during study formulation therapy. Liver function tests did not show any statistically significant difference (baseline vs. week 4). Concerning efficacy, there was a statistically significant difference between baseline, month 1, and month 3 in the OSDI (Ocular Surface Disease Index) test results in both treatment groups (group A and group A + L). Furthermore, both groups showed statistically significant differences between baseline and month 3 regarding the non-invasive film tear breakup time (NIF-BUT) score and a positive trend related to Shirmer's test at month 3. The non-invasive average breakup time (NIAvg-BUT) score showed a statistically significant difference at month 3 when compared with baseline in the A + L group. The P + L group showed a statistically significant difference in terms of the OSDI questionary between baseline and month 3. Regarding the lissamine green staining, the A + L group showed a statistical difference between baseline and month 3 (p = 0.0367). The placebo + lubricant group did not show statistically significant differences. Finally, the placebo group did not show any data with statistically significant differences. Consequently, this polyphenol formulation as a primary treatment outperformed the placebo alone, and the polyphenol oral formulation used as an adjuvant to artificial tears was superior to the combination of the placebo and the artificial tears. Thus, our data strongly suggest that this polyphenol oral formulation improves visual strain symptoms and tear film status in patients with mild to moderate DED.

Phytochemical Profile and Antioxidant and Antiproliferative Activity of Sedum dendroideum on Pterygium Fibroblasts.

BACKGROUND: Sedum dendroideum has antioxidant effects that are beneficial for different diseases. We aimed to analyze the antiproliferative activity of S. dendroideum in human pterygium fibroblasts (HPFs). METHODS: HPFs were treated for 24 h with 0-1000 µg/mL of S. dendroideum lyophilized to analyze its effect on cell viability using the CellTiter assay. RNA from HPF treated with 250 µg/mL of S. dendroideum lyophilized was isolated, and the expression of VEGF and CTGF genes was evaluated by qPCR. A dermal fibroblast cell line (HDFa) was used as a healthy control. The total phenolic content, antioxidant activity, and chemical profile of S. dendroideum lyophilized were determined. RESULTS: Viability of HPF decreased after 24 h treatment of S. dendroideum in a dose-dependent manner. The expression of VEGF and CTGF significantly decreased (P < 0.01) in HPF treated with 250 µg/mL of S. dendroideum when compared with untreated HPF. The total phenolic concentration in the S. dendroideum lyophilized was 33.67 mg gallic acid equivalents (GAE)/g. Antioxidant activity was 384.49 mM Trolox equivalents/mL. The main phenolic compounds identified by HPLC analysis were the kaempferol-3-O-glycoside, kaempferol-3-O-rhamnoside, kaempferol-3-O-neohesperidoside-7-O-α-rhamnopyranoside, and kaempferol-3-O-glycoside-7-O-rhamnoside. CONCLUSIONS: S. dendroideum decreases the proliferation of HPF and the expression of VEGF and CTGF. The phenolic compound concentration, antioxidant activity, and phytochemical profile may play a role in these effects.

COVID-19 and the eye: a review.

BACKGROUND: To provide a review for general practitioners and medical specialists about the most common eye complaints and ocular manifestations in a COVID-19 patient. METHODS: Reviewed 50 articles referenced in 4 databases from 20 December 2019 to 16 September 2020. RESULTS: Of the 50 articles reviewed, 26 met the criteria for analysis and were included in the study. Among them were 5 reviews, 6 case series, 7 case reports, 4 cross-sectional studies, 2 systematic reviews, 1 cohort study and 1 correspondence. We found that the prevalence of ocular manifestations in patients during the course of COVID-19 varied between 0.8% and 31.6%, depending on the study design. Symptoms of acute conjunctivitis were the most frequent clinical findings. Acute phase reactants were also correlated to ocular manifestations and the severity of the systemic disease in many reports. CONCLUSIONS: Ocular manifestations are not uncommon in COVID-19 patients and have been associated with higher levels of acute phase reactants as well as a higher degree of severity of the systemic disease. We recommend that all physicians consider COVID-19 as a differential diagnosis in the presence of acute conjunctivitis with or without systemic symptoms.

Arresting proliferation improves the cell identity of corneal endothelial cells in the New Zealand rabbit.

Purpose: Corneal endothelium engineering aims to reduce the tissue shortage for corneal grafts. We investigated the impact of mitogenic and resting culture systems on the identity of corneal endothelial cells (CECs) for tissue engineering purposes. Methods: Rabbit CECs were cultured in growth factor-supplemented media (MitoM) until confluence. At the first passage, the CECs were divided into two populations: P1 remained cultured in MitoM, and P2 was cultured in a basal medium (RestM) for another passage. Morphologic changes in the CECs were analyzed, and RNA was isolated for transcriptome analysis. Quantitative PCR and immunocytochemistry validation of selected differentially expressed markers were performed. Results: The CECs in MitoM showed fibroblastic morphology, whereas the CECs in RestM exhibited polygonal morphology. Circularity analysis showed similar values in human (0.75±0.056), rabbit basal (before cultured; 0.77±0.063), and CECs in RestM (0.73±0.09), while MitoM showed lower circularities (0.41±0.19). Genes related to collagen type IV and the extracellular matrix, along with the adult CEC markers ATP1A1, ATP1B1, COL8A2, GPC4, and TJP1, were highly expressed in RestM. Conversely, the IL-6, F3, and ITGB3 genes and the non-adult CEC markers CD44, CNTN3, and CD166 were more expressed in MitoM. Overall, from the transcriptome, we identified 832 differentially expressed probes. A functional analysis of the 308 human annotated differentially expressed genes revealed around 13 functional clusters related to important biological terms, such as extracellular matrix, collagen type 4, immune responses, cell proliferation, and wound healing. Quantitative PCR and immunocytochemistry confirmed the overexpression of ATP1A1, TJP1, and GPC4 in CECs in RestM. Conclusions: The addition of a stabilization step during CEC culture improves the cells' morphology and molecular identity, which agrees with transcriptome data. This suggests that stabilization is useful for studying the plasticity of the corneal endothelium's morphology, and stabilization is proposed as a necessary step in corneal endothelium engineering.

Valor percibido de una experiencia de inmersión educativa para el desarrollo de competencias trasversales: Semana i / Perceived value from immersion educational experience for the development of transversal competences: I Week

INTRODUCCIÓN: Actualmente las instituciones educativas cuentan con el desafío de egresar alumnos no solo como expertos en sus disciplinas, sino que además cuenten con competencias transversales que les permitirán adaptarse a entornos profesionales y personales en el futuro. La Escuela de Medicina y Ciencias de la Salud del Tecnológico de Monterrey, como parte de su Modelo Educativo Tec21, ha establecido la total inmersión en actividades retadoras durante la Semana i, como una de las iniciativas para desarrollar las competencias en sus programas educativos de profesional. OBJETIVO: Determinar el valor percibido de la Semana I por parte de los alumnos en el desarrollo de las competencias transversales del Modelo Tec21 a nivel individual, interpersonal, organizacional y sistémico. METODOLOGÍA: Se utiliza un método cuantitativo, descriptivo, transeccional y no experimental. Se diseñaron 2 instrumentos de autorreflexión sobre las competencias del Modelo Tec21. El primero mide las expectativas y las preferencias de los alumnos a modo de pretest. El segundo mide los logros de la Semana I a modo de postest. Se utilizaron grupos de enfoque y pruebas de confiabilidad para su validación. El valor percibido se calcula como la diferencia entre los resultados del pretest y el postest. RESULTADOS: Las competencias individuales e interpersonales son las que se consideraron con valor percibido significativo por los estudiantes durante la Semana I CONCLUSIONES: Se vuelve indispensable reconsiderar el diseño de las actividades para aportar valor a lasorganizaciones y sociedad en general

INTRODUCTION: Educational institutions currently have the responsibility to educate students, not only as experts in their disciplines, but also with transversal competences to support them in future professional and personal environments. The School of Medicine and Health Sciences and Technology of Monterrey, as part of its Educational Tec21 Model, has established total immersion challenging activities during the I Week, as one of the initiatives to develop transversal competencies for undergraduate programs. OBJECTIVE: To identify the perceived value of I Week by the students in the development of Tec21 Model transversal competences at individual, interpersonal, organisational, and systemic level. METHODOLOGY: A quantitative, descriptive, cross-sectional and non-experimental method was conducted using 2 specifically designed questionnaires for self-reflection on the competences of the Tec21 Model. The first one measured the expectations and preferences of the students as a pre-test. The second one measured the achievements of I Week as a post-test. Focus groups and reliability tests were used for validation. The perceived value is calculated as the difference between the results of the pre-test and post-test. RESULTS: Individual and interpersonal competences were considered with a significant perceived value by students during I Week. CONCLUSIONS: It becomes essential to reconsider the design of activities to add value to organizations and society in general

Aprendizaje basado en retos: una experiencia de innovación para enfrentar problemas de salud pública / Challenge based learning: Innovation experience to solve healthcare problems

INTRODUCCIÓN: El aprendizaje basado en retos es una experiencia donde los participantes desarrollan soluciones que requieren un abordaje interdisciplinario y creativo para el desarrollo de competencias transversales. Con este enfoque se realizó la Semana i: Retos de innovación enfrentando problemas de salud, programa de inmersión donde estudiantes de medicina acudieron al Parque de Investigación e Innovación Tecnológica para plantear soluciones a 10 problemas de salud pública (cáncer, diabetes y salud mental, entre otros) a partir de conocimiento no médico. MATERIAL Y MÉTODO: El objetivo de este estudio fue evaluar las competencias de pensamiento crítico y creativo al finalizar el programa. Esta investigación incorporó un abordaje cuantitativo, mediante un estudio descriptivo y transeccional, en el que cada equipo fue evaluado por 3 personas, en las variables de explicación, inferencia e interpretación, para el pensamiento crítico, y propuesta, rediseño e invención, para el creativo. RESULTADOS: Se utilizó una escala Likert de 1 (regular) a 3 (excelente). Los mejores desempeños fueron explicación (2,65) y propuesta (2,53). DISCUSIÓN: Se requiere mejorar el desarrollo de la autorregulación en los estudiantes para superar la frustración de adentrarse en un campo disciplinar diferente

INTRODUCTION: Challenge based learning is an experience where the participants develop solutions that require an interdisciplinary and creative approach for the development of general skills. This focus was developed in a health innovation week challenge, an immersive program where medical students visited the Technology Research and Innovation Park to generate solutions to 10 public health problems (cancer, diabetes, and mental health, among others) based on non-medical knowledge. MATERIAL AND METHOD: The aim of the study was to assess the skills of critical and creative thinking at the end of the program. The study included a quantitative analysis of a descriptive and cross-sectional study, in which each team was rated by 3 judges, in the variables of explanation, inference and interpretation, for critical thinking, and proposal, redesign, and invention for the creative. RESULTS: A Likert scale was used to assess each variable from 1 (regular) to 3 (excellent). The best performances were explanation (2.65) and proposal (2.53). DISCUSSION: It is concluded that the experience needs to improve in the development of self-regulation in students, in order to overcome the frustration of entering into a different disciplinary field