Dry eye disease pathogenesis and clinical signs: searching for correspondence in the clinical practice.

BACKGROUND: Ocular surface alterations causing dry eye disease (DED) can be described as a vicious circle consisting of different consecutive stages. Among the factors involved, the ocular surface immune-inflammatory response has been established as a key player in the pathogenesis of the vicious circle of DED. Thus, the prompt recognition of the disruption of the immunoregulatory mechanisms is crucial for properly managing the ocular surface alterations. To increase awareness and knowledge of the identification and clinical interpretation of immunological mechanisms of dry eye in clinical practice, we present two clinical cases related to DED patients to provide a practical example of clinical examination application and interpretation of diagnostic parameters in daily practice. Moreover, a literature overview of the available clinical examinations to assess the immunological involvement in DED patients, with a particular focus on the correlation between diagnostic parameters and pathogenesis of clinical signs, is provided with an educational intent. CASE PRESENTATION: The presented clinical experiences suggested that in ocular surface pathologies, knowledge of the immune-inflammatory pathogenetic mechanisms underlying the observed clinical sign is of great help for understanding what is being observed in the patient and, consequently, for the choice of appropriate therapy. Literature evidence suggests that many different clinical examinations can be used to assess inflammation in DED patients, such as the assessment of hyperemia, staining of the ocular surface and measurement of hyperosmolarity and MMP-9 levels. The combination of impression cytology and flow cytometry to assess for markers of inflammation is considered the best technique to quantify the level of inflammation on the ocular surface, even if not always applicable in clinical practice. CONCLUSIONS: Literature evidence and clinical experiences suggest that basic diagnostic approaches (assessment of hyperemia, MMP-9 levels, and staining of the ocular surface with Lissamine green or fluorescein) represent useful tools to assess the inflammatory component of DED in everyday practice, providing a guide to establish the correct therapeutic strategy.

Corneal endothelial validation in the eye bank: differences in automated methods and repeatability.

PURPOSE: To evaluate reproducibility of endothelial cell density (ECD) measurements using the Konan Cell Check D in donor corneas by two different ophthalmologists and to compare the two automated cell count methods (center and flex-center) available in the software of this specular microscope. METHODS: ECD values were quantified in 54 donor corneas by two independent investigators using the Cell Check D (Konan Medical USA Inc) with both automated cell count methods. In the center method, at least 30 contiguous cells are marked. For the flex-center method, an area is delineated and only the cells within the designated area are counted. RESULTS: The mean ECD was 2473.81±378.22 cells/mm2. Good ECD intergrader reproducibility for the center (ICC=0.821) and the flex-center method (ICC=0.784) were noted. Poor reliability was observed for coefficient of variation and hexagonality (ICC≤0.265). When both methods for ECD analysis were compared, a moderate correlation for the two independent graders using the two manual (center and flex-center) methods was detected (correlation coefficient of 0.678 and 0.745 for each of the investigators). Comparison between methods yielded significantly higher ECD with the flex-center method (P=0.013). When corneas were divided by ECD, those under 2200 cells/mm2 and those between 2200 and 2700 cells/mm2 also had significantly higher ECD with the flex-center method (P<0.022). CONCLUSIONS: ECD values are reproducible with both methods, although the flex-center method ECDs tend to be higher, particularly in cases of low ECD. Eye banks and surgeons should exercise caution in making decisions based only on small differences in ECD.

New trends towards glaucoma treatment: Topical osmoprotective microemulsions loaded with latanoprost.

The chronic use of hypotensive agents eventually leads to ocular surface damage and poor patient compliance during glaucoma management. Thus, new sustained drug delivery systems are needed. This work aimed to develop osmoprotective latanoprost-loaded microemulsion formulations as new potential glaucoma treatments with ocular surface protective properties. The microemulsions were characterized and latanoprost encapsulation efficacy determined. In-vitro tolerance, osmoprotective efficacy, cell internalization as well as cell-microemulsion interactions and distribution were performed. In vivo hypotensive activity was conducted in rabbits to assess intraocular pressure reduction and relative ocular bioavailability. Physicochemical characterization showed nanodroplet sizes within 20-30 nm, being in vitro tolerance within 80 and 100% viability in corneal and conjunctival cells. Besides, microemulsions exhibited higher protection under hypertonic conditions than untreated cells. Cell fluorescence lasted for 11 days after short exposure to coumarin-loaded microemulsions (5 min) showing extensive internalization in different cell compartments by electronic microscopy. In vivo studies exhibited that a single instillation of latanoprost-loaded microemulsions reduced the intraocular pressure for several days (4-6 days without polymer and 9-13 days with polymers). Relative ocular bioavailability was 4.5 and 19 times higher than the marketed formulation. These findings suggest the use of these microemulsions as potential combined strategies for extended surface protection and glaucoma treatment.

Quejas visuales durante la pandemia de COVID-19 en España y Portugal / Visual complaints during the COVID-19 pandemic in Spain and Portugal

Objetivo Este estudio reporta los hábitos de la población y las quejas oculares relacionadas con la salud visual en el contexto de la pandemia de COVID-19 a partir de visitas realizadas durante 2021 en España y en Portugal. Material y métodos Invitación por correo electrónico a una encuesta transversal online y también realizada en persona a pacientes de clínicas de oftalmología de España y de Portugal de septiembre a noviembre de 2021. Participaron 3.833 encuestados mayores de 18años con respuestas anónimas válidas. Resultados El 60% de los encuestados explicó mucha incomodidad causada por el aumento de los síntomas de ojo seco debido al trabajo digital más intenso y el empañamiento de los lentes al usar mascarillas. El 81,6% de los encuestados usaba dispositivos digitales al menos 3horas en promedio por día, y el 40% comenzó a usar dispositivos digitales más de 8horas en promedio por día. Además, el 44% de los encuestados sintió que su visión de cerca había empeorado en este período. El primer síntoma importante de la presbicia estaba relacionado con la dificultad para leer las letras más pequeñas de los paquetes. El 86% presentó los primeros síntomas a los 40años. Las ametropías más frecuentes identificadas fueron miopía (40,2%) y astigmatismo (36,7%). Para los padres, tener buena vista (87,2%) era el aspecto más valorado en la vida de sus hijos. Conclusiones Los hallazgos brindan una idea de los desafíos durante la COVID-19 para las prácticas oftalmológicas. En una sociedad altamente dependiente de la visión, es fundamental centrarse en los signos y los síntomas que conducen a afecciones oftalmológicas. El uso excesivo de dispositivos digitales y el uso de mascarillas durante esta pandemia han agravado algunos, señalando la importancia de la referencia para planificar una atención ocular eficiente en situaciones similares (AU)

Purpose This study reports visual health during the COVID-19 pandemic in 2021 in Spain and Portugal, focusing on eye complaints and population habits. Material and methods Cross-sectional survey through an online email invitation to patients attending ophthalmology clinics in Spain and Portugal from September to November 2021. Around 3833 participants offered valid anonymous responses in a questionnaire. Results Sixty percent of respondents identified significant discomfort related to dry eye symptoms for increased screen time and lens fogging using facemasks. 81.6% of the participants used digital devices for more than 3h per day and 40% for more than 8h. In addition, 44% of participants referred to worsening near vision. The most frequent ametropias were myopia (40.2%) and astigmatism (36.7%). Parents considered eyesight the most important aspect of their children (87.2%). Conclusions The results show the challenges for eye practices during the initial COVID-19 pandemic. Focusing on signs and symptoms that lead to ophthalmologic conditions is an essential concern, especially in our digital society highly dependent on vision. At the same time, the excessive use of digital devices during this pandemic has aggravated dry eye and myopia (AU)

[Visual complaints during the COVID-19 pandemic in Spain and Portugal]. / Quejas visuales durante la pandemia de COVID-19 en España y Portugal.

Purpose: This study reports visual health during the COVID-19 pandemic in 2021 in Spain and Portugal, focusing on eye complaints and population habits. Material and methods: Cross-sectional survey through an online email invitation to patients attending ophthalmology clinics in Spain and Portugal from September to November 2021. Around 3833 participants offered valid anonymous responses in a questionnaire. Results: Sixty percent of respondents identified significant discomfort related to dry eye symptoms for increased screen time and lens fogging using facemasks. 81.6% of the participants used digital devices for more than 3 h per day and 40% for more than 8 h. In addition, 44% of participants referred to worsening near vision. The most frequent ametropias were myopia (40.2%) and astigmatism (36.7%). Parents considered eyesight the most important aspect of their children (87.2%). Conclusions: The results show the challenges for eye practices during the initial COVID-19 pandemic. Focusing on signs and symptoms that lead to ophthalmologic conditions is an essential concern, especially in our digital society highly dependent on vision. At the same time, the excessive use of digital devices during this pandemic has aggravated dry eye and myopia.

Visual complaints during the COVID-19 pandemic in Spain and Portugal.

PURPOSE: This study reports visual health during the COVID-19 pandemic in 2021 in Spain and Portugal, focusing on eye complaints and population habits. MATERIAL AND METHODS: Cross-sectional survey through an online email invitation to patients attending ophthalmology clinics in Spain and Portugal from September to November 2021. Around 3833 participants offered valid anonymous responses in a questionnaire. RESULTS: Sixty percent of respondents identified significant discomfort related to dry eye symptoms for increased screen time and lens fogging using facemasks. 81.6% of the participants used digital devices for more than 3 h per day and 40% for more than 8 h. In addition, 44% of participants referred to worsening near vision. The most frequent ametropias were myopia (40.2%) and astigmatism (36.7%). Parents considered eyesight the most important aspect of their children (87.2%). CONCLUSIONS: The results show the challenges for eye practices during the initial COVID-19 pandemic. Focusing on signs and symptoms that lead to ophthalmologic conditions is an essential concern, especially in our digital society highly dependent on vision. At the same time, the excessive use of digital devices during this pandemic has aggravated dry eye and myopia.

Estudio IMPULSO: impacto de la COVID-19 en el presente de la oftalmología centrada en superficie ocular y tendencias de futuro / IMPULSE Study: Impact of COVID-19 in the present of ophthalmology focusing on ocular surface and future trends

Antecedentes y objetivo La evolución digital supone una oportunidad para que la oftalmología se adapte a nuevos modelos asistenciales. Este estudio tuvo como objetivo conocer cómo la pandemia ha modificado la práctica clínica y actividades formativas del oftalmólogo especializado en superficie ocular, y analizar tendencias y necesidades emergentes. Materiales y métodos Estudio realizado mediante encuesta online. Un comité de 3 especialistas diseñó un cuestionario de 25 preguntas estructurado en: 1) Perfil del participante; 2) Impacto de la pandemia en el manejo del paciente y las actividades profesionales; 3) Tendencias y necesidades. Resultados Participaron 68 oftalmólogos clínicos. Hubo un alto grado de acuerdo (90%) en que la pandemia demoró las visitas de seguimiento oftalmológico y el diagnóstico. Los participantes coincidieron en que aumentó la frecuencia de pacientes con enfermedad de ojo seco (75%), orzuelo/chalazión (62%) y blefaritis (60%). Según un 28%, será habitual el teleseguimiento mediante teleconsulta de dolencias como ojo seco, glaucoma, diabetes, conjuntivitis, hiposfagmas, orzuelos, etc., especialmente en población joven. Esto será especialmente relevante en las enfermedades crónicas o leves de la superficie ocular, y en el seguimiento de pacientes tras operación de cataratas y retinopatía diabética. Conclusiones Durante la pandemia se ha percibido un aumento de la incidencia de ciertas enfermedades de superficie ocular. El seguimiento de enfermedades crónicas o leves de la superficie ocular se vincula a la necesidad de proporcionar formación específica tanto para el paciente como para el profesional que lo atiende, además de protocolos de cribado y derivación que optimicen el flujo asistencial (AU)

Background and objective Digital evolution represents an opportunity for ophthalmology to adapt to new care models. This study aimed to find out how the pandemic has modified the clinical practice and training activities of the ophthalmologist specialized in ocular surface, as well as to analyze emerging trends and needs. Materials and methods This study was carried out through an online survey. A committee of 3 specialists developed a questionnaire of 25 questions structured in: 1) Participant profile; 2) Impact of the pandemic on patient management and professional activities; 3) Trends and needs. Results Sixty-eight clinical ophthalmologists participated. There was a high degree of agreement (90%) that the pandemic has delayed ophthalmological follow-up visits and diagnosis. The participants agreed that the frequency of patients with dry eye disease (75%), stye/chalazion (62%) and blepharitis (60%) has increased. According to 28%, remote monitoring of pathologies such as dry eye, glaucoma, diabetes, conjunctivitis, hyposphagmas, styes, etc., will be common, especially in the young population. This will be especially relevant in chronic or mild pathologies of the ocular surface, and in the follow-up of patients after cataract and diabetic retinopathy interventions. Conclusions During the pandemic, an increase in the incidence of certain ocular surface diseases has been perceived. The telematic follow-up of chronic or mild pathologies of the ocular surface entails the need to provide specific training for both the patient and the healthcare professional, in addition to screening and referral protocols that would optimize the flow of care (AU)

IMPULSE Study: Impact of COVID-19 in the present of ophthalmology focusing on ocular surface and future trends.

INTRODUCTION AND OBJECTIVE: Digital evolution represents an opportunity for ophthalmology to adapt to new care models. This study aimed to find out how the pandemic has modified the clinical practice and training activities of the ophthalmologist specialised in ocular surface, as well as to analyse emerging trends and needs. MATERIALS AND METHODS: This study was carried out through an online survey. A committee of 3 specialists developed a questionnaire of 25 questions structured in: 1) Participant profile; 2) Impact of the pandemic on patient management and professional activities; 3) Trends and needs. RESULTS: 68 clinical ophthalmologists participated. There was a high degree of agreement (90%) that the pandemic has delayed ophthalmological follow-up visits and diagnosis. The participants agreed that the frequency of patients with dry eye disease (75%), stye/chalazion (62%) and blepharitis (60%) has increased. According to 28%, remote monitoring of pathologies such as dry eye, glaucoma, diabetes, conjunctivitis, hyposphagmas, styes, etc., will be common, especially in the young population. This will be especially relevant in chronic or mild pathologies of the ocular surface, and in the follow-up of patients after cataract and diabetic retinopathy interventions. CONCLUSIONS: During the pandemic, an increase in the incidence of certain ocular surface diseases has been perceived. The telematic follow-up of chronic or mild pathologies of the ocular surface entails the need to provide specific training for both the patient and the healthcare professional, in addition to screening and referral protocols that would optimise the flow of care.

[IMPULSE Study: Impact of COVID-19 in the present of ophthalmology focusing on ocular surface and future trends]. / Estudio IMPULSO: impacto de la COVID-19 en el presente de la oftalmología centrada en superficie ocular y tendencias de futuro.

Background and objective: Digital evolution represents an opportunity for ophthalmology to adapt to new care models. This study aimed to find out how the pandemic has modified the clinical practice and training activities of the ophthalmologist specialized in ocular surface, as well as to analyze emerging trends and needs. Materials and methods: This study was carried out through an online survey. A committee of 3 specialists developed a questionnaire of 25 questions structured in: 1) Participant profile; 2) Impact of the pandemic on patient management and professional activities; 3) Trends and needs. Results: Sixty-eight clinical ophthalmologists participated. There was a high degree of agreement (90%) that the pandemic has delayed ophthalmological follow-up visits and diagnosis. The participants agreed that the frequency of patients with dry eye disease (75%), stye/chalazion (62%) and blepharitis (60%) has increased. According to 28%, remote monitoring of pathologies such as dry eye, glaucoma, diabetes, conjunctivitis, hyposphagmas, styes, etc., will be common, especially in the young population. This will be especially relevant in chronic or mild pathologies of the ocular surface, and in the follow-up of patients after cataract and diabetic retinopathy interventions. Conclusions: During the pandemic, an increase in the incidence of certain ocular surface diseases has been perceived. The telematic follow-up of chronic or mild pathologies of the ocular surface entails the need to provide specific training for both the patient and the healthcare professional, in addition to screening and referral protocols that would optimize the flow of care.

Development of an osmoprotective microemulsion as a therapeutic platform for ocular surface protection.

Self-emulsified osmoprotective ophthalmic microemulsions (O/A) were prepared by combining betaine/leucine, clusterin/oleanolic acid, and hyaluronic acid or Dextran. The microemulsions contained an internal oily phase (1.2%), an external aqueous phase (96.3%), cosolvents (1%), and surfactants (1.5%). Physicochemical characterization and in vivo and in vitro tolerance were analyzed. The formulations' osmoprotective in vitro activity was assayed in a hyperosmolar model in human corneal cells. Average internal phase sizes were 16-26 nm for the microemulsions including Dextran. Addition of hyaluronic acid increased the size range (25-39 nm). Addition of osmoprotectants did not change nanodroplet size. The formulations were isotonic (280-290 mOsm/L) with neutral pH (≈7) and zeta potential (-10 to 0 mV), low surface tension (≈35-40mN·m-1), and low viscosity (≈1 mPa·s), except for the microemulsions containing hyaluronic acid (≈4-5 mPa·s). SEM and cryo-TEM showed that all formulations exhibited sphere-shaped morphology with good cell tolerance (≈100%) and were stable at 8 °C for 9 months. Osmoprotective formulations were well tolerated in vitro and in vivo, protecting cells from hypertonic stress. We therefore developed stable microemulsions compatible with the ocular surface that could constitute a novel tool for treatment of ophthalmic diseases.

Hypochlorous acid as an antiseptic in the care of patients with suspected COVID-19 infection.

PURPOSE: The SARS-CoV-2 virus, which causes COVID-19 disease, is transmitted by aerosols or by contact with infected surfaces. The route of entry to the body is through the nasal, oral or conjunctival mucosa. Health workers must use effective protection measures against the entry of the virus into mucous membranes, both physical and antiseptic filters. There is an antiseptic used in Ophthalmology that we believe could have virucidal action against the SARS-CoV-2 virus, formulated based on 0.01% hypochlorous acid. METHODS: An exhaustive search has been carried out in the databases of Pubmed and Web of Science to identify relevant articles on the virucidal activity of hypochlorous acid in different concentrations until October 4, 2020. RESULTS: There is evidence of the virucidal efficacy of 0.01% hypochlorous acid against SARS-CoV-2. According to the different scientific publications reviewed, hypochlorous acid has virucidal efficacy against different viruses, among them, SARS-CoV-2. CONCLUSIONS: The 0.01% hypochlorous acid could act as an effective antiseptic against SARS-CoV-2, exerting a barrier on the mucosa to prevent COVID-19 infection. It can be used on the eyes, nose and mouth. We consider it necessary to assess its use in the protocol for patient health care in ophthalmology consultations, as well as to recommend its use to the general population to reduce viral load and/or prevent transmission of infection. Additional in vivo studies would be required to confirm its antiseptic action.

Ácido hipocloroso como antiséptico en la atención al paciente con sospecha de infección por COVID-19 / Hypochlorous acid as an antiseptic in the care of patients with suspected COVID-19 infection

PropósitoEl virus SARS-CoV-2, causante de la enfermedad COVID-19, se transmite por aerosoles o por contacto con superficies infectadas. La ruta de entrada al cuerpo se produce a través de la mucosa nasal, oral o conjuntival. El personal sanitario debe usar medidas de protección efectivas a la entrada del virus en mucosas, tanto filtros físicos como antisépticos. Uno de los antisépticos usados en oftalmología, formulado a base de ácido hipocloroso al 0,01%, consideramos que podría tener acción virucida frente al virus SARS-CoV-2. El objetivo del estudio fue revisar la evidencia científica sobre la actividad virucida del ácido hipocloroso frente al SARS-CoV-2.MétodosSe realizó una búsqueda exhaustiva en las bases de datos de Pubmed y Web of Science para identificar artículos relevantes sobre la actividad virucida del ácido hipocloroso en diferentes concentraciones, publicados hasta el 4 de octubre de 2020.ResultadosLa búsqueda arrojó un total de 20 artículos. Los estudios analizados mostraron pruebas de la eficacia virucida del ácido hipocloroso, a una concentración del 0,01%, frente al SARS-CoV-2, así como frente a otros virus.ConclusionesEl ácido hipocloroso al 0,01% podría actuar como antiséptico eficaz frente al SARS-CoV-2, creando una barrera protectora sobre las mucosas para evitar la entrada del virus y el desarrollo de la infección COVID-19. El producto puede ser aplicado en ojos, nariz y boca, sin efectos nocivos. Por ello, consideramos necesario valorar su uso en el protocolo de atención sanitaria al paciente en consultas de oftalmología, así como recomendar su uso a la población general para disminuir la carga viral y/o evitar transmisión de la infección. No obstante, se requerirían estudios adicionales in vivo para confirmar su acción virucida.

PurposeThe SARS-CoV-2 virus, which causes COVID-19 disease, is transmitted by aerosols or by contact with infected surfaces. The route of entry to the body is through the nasal, oral or conjunctival mucosa. Health workers must use effective protection measures against the entry of the virus into mucous membranes, both physical and antiseptic filters. There is an antiseptic used in Ophthalmology that we believe could have virucidal action against the SARS-CoV-2 virus, formulated based on 0.01% hypochlorous acid.MethodsAn exhaustive search has been carried out in the databases of Pubmed and Web of Science to identify relevant articles on the virucidal activity of hypochlorous acid in different concentrations until October 4, 2020.ResultsThere is evidence of the virucidal efficacy of 0.01% hypochlorous acid against SARS-CoV-2. According to the different scientific publications reviewed, hypochlorous acid has virucidal efficacy against different viruses, among them, SARS-CoV-2.ConclusionsThe 0.01% hypochlorous acid could act as an effective antiseptic against SARS-CoV-2, exerting a barrier on the mucosa to prevent COVID-19 infection. It can be used on the eyes, nose and mouth. We consider it necessary to assess its use in the protocol for patient health care in ophthalmology consultations, as well as to recommend its use to the general population to reduce viral load and / or prevent transmission of infection. Additional in vivo studies would be required to confirm its antiseptic action.

[Hypochlorous acid as an antiseptic in the care of patients with suspected COVID-19 infection]. / Ácido hipocloroso como antiséptico en la atención al paciente con sospecha de infección por COVID-19.

PURPOSE: The SARS-CoV-2 virus, which causes COVID-19 disease, is transmitted by aerosols or by contact with infected surfaces. The route of entry to the body is through the nasal, oral or conjunctival mucosa. Health workers must use effective protection measures against the entry of the virus into mucous membranes, both physical and antiseptic filters. There is an antiseptic used in Ophthalmology that we believe could have virucidal action against the SARS-CoV-2 virus, formulated based on 0.01% hypochlorous acid. METHODS: An exhaustive search has been carried out in the databases of Pubmed and Web of Science to identify relevant articles on the virucidal activity of hypochlorous acid in different concentrations until October 4, 2020. RESULTS: There is evidence of the virucidal efficacy of 0.01% hypochlorous acid against SARS-CoV-2. According to the different scientific publications reviewed, hypochlorous acid has virucidal efficacy against different viruses, among them, SARS-CoV-2. CONCLUSIONS: The 0.01% hypochlorous acid could act as an effective antiseptic against SARS-CoV-2, exerting a barrier on the mucosa to prevent COVID-19 infection. It can be used on the eyes, nose and mouth. We consider it necessary to assess its use in the protocol for patient health care in ophthalmology consultations, as well as to recommend its use to the general population to reduce viral load and / or prevent transmission of infection. Additional in vivo studies would be required to confirm its antiseptic action.

Aniridia and the ocular surface: Medical and surgical problems and solutions.

Congenital aniridia is a multisystemic genetic disease due to a mutation in PAX6 gene which severely affects the development and functionality of the human eyes. In patients affected by the mutation, aside from the absence or defects of iris tissue formation, abnormalities in position or opacities of the crystalline lens, macular hypoplasia, ocular surface disease is the main cause of visual loss and the deterioration of the quality of life of most patients. Limbal stem cell deficiency combined with tear film instability and secondary dry eye cause aniridic keratopathy which, in advanced stages, ends up in corneal opacification. In this paper, the actual knowledge about congenital aniridia keratopathy physiopathology and medical and surgical treatment options and their efficacy are discussed. Indications and results of topical treatments with artificial tears and blood-derivatives in its initial stages, and different surgical techniques as limbal stem cell transplantation, keratoplasty and keratoprostheses are reviewed. Finally, recent advances and results in regenerative medicine techniques with ex vivo stem cell cultivation or other types of cultivated cells are presented.

Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments.

PURPOSE: To develop an easy-to-perform combined model in human corneal epithelial cells (HCECs) and Balb/c mice macrophages J774.A1 (MP) for preliminary screening of potential ophthalmic therapeutic substances. METHODS: HCECs were exposed to different osmolarities (350-500 mOsm/L) and MTT assay was employed for cell survival and flow cytometry to assess apoptosis-necrosis and relative cell size (RCS) distribution. Effectiveness of Betaine, L-Carnitine, Taurine at different concentrations (ranging from 20 mM to 200 mM) was studied. Also, mucoadhesive polymers such as Hyaluronic acid (HA) and Hydroxypropylmethylcellulose (HPMC) (0.4 and 0.8%) were evaluated. Cells were pre-incubated with the compounds (8h) and then exposed to hyperosmotic stress (470 mOsm/L) for 16h. Moreover, anti-inflammatory activity was performed in LPS-stimulated MP. RESULTS: Exposure to hyperosmotic solutions between 450 and 500 mOsm/L promoted the highest cell death after 16h exposures (p < 0.0001) with a drop in viability to 34.96% ± 11.77 for 470 mOsm/L. Pre-incubation with Betaine at 150 mM and 200 mM provided the highest cell survival against hyperosmolarity (66.01% ± 3.65 and 65.90% ± 0.78 respectively) while HA 0.4% was the most effective polymer in preventing cell death (42.2% ± 3.60). Flow cytometry showed that Betaine and Taurine at concentrations between 150-200 mM and 20-80 mM respectively presented the highest anti-apoptotic activity. Also, HA and HPMC polymers reduced apoptotic-induced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. L-Carnitine 50 mM, Taurine 40 mM and HA 0.4% presented the highest TNF-α inhibition activity (60%) albeit all of them showed anti-inflammatory inhibition percentages higher than 20% CONCLUSIONS: HCECs hyperosmolar model combined with inflammatory conditions in macrophages allows the screening of osmoprotectants by simulating chronic hyperosmolarity (16h) and inflammation (24h).

A new standardised nomenclature in ophthalmology: Criteria and quantitative evaluation indicators of medical procedures. / Nuevo nomenclátor estandarizado en oftalmología: Criterios e indicadores cuantitativos de baremación de actos médicos.

PURPOSE: To create a new list of medical procedures in ophthalmology based on the International Classification of Diseases ICD-9-CM. To establish the general principles that define criteria, quantitative indicators, and scales. To develop the algorithms needed to calculate fees for medical procedures. METHODS: The out-of-date processes were removed from the list, and new techniques were added, descriptors were modified, procedures with similar descriptions were grouped together, and others were relocated to other group according to surgical complexity conditions. The criteria to calculate the medical fees were defined: training and complexity (U), proficient responsibility (R), and health value (V), with their respective quantitative indicators: period of training necessary to master a technique, frequency of complications that worsen the preoperative situation, and days of incapacity for work due to the process. The Relative Value Unit (RVU) was defined as the score sum of R, V and U. The final fee per medical procedure was calculated as the product of the RVU by its unit cost and by the weighting coefficient (WC). RESULTS: A new catalogue was prepared with 161 medical procedures, grouped into consultations, diagnostic procedures (DX.PR), therapeutic procedures (TX.PR), and surgical interventions, increasing in complexity from group 0 to group 8. The following characters were described for each one of the procedures: OMC and ICD-9-MC code, descriptor term, group, proposed modification: no changes or minimums in the descriptors, grouping of acts by similar definitions, change of origin group, new procedures, and procedures removed. The indicators for assessment were also scored: U between 1-4 points, and R and V between 0-3 points. Using their sum, the number of RVUs per medical procedure (between 1 and 10) was calculated which, together with the unit cost of the RVU and the WC (between 0.05 and 1), will determine the final rate. CONCLUSIONS: The new standardised ophthalmological nomenclature updates and improves the old classification, adapting the procedures to the descriptors included in the ICD-9-CM, and incorporating all the new techniques. Additionally, the declaration of the general principles allows defining new criteria, quantitative indicators, rating scales, and algorithms to calculate fees for medical procedures.

Dry eye disease treatment: the role of tear substitutes, their future, and an updated classification.

OBJECTIVE: The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes. MATERIALS AND METHODS: A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting. RESULTS: The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology. CONCLUSIONS: Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.