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.

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.

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.

Resultados y evolución histórica de las redes sociales en el American College of Surgeons Clinical Congress y el Congreso Nacional de Cirugía. Análisis del #ACSCC20 y #CNCirugia2020 / Trends of social networks in the American College of Surgeons Clinical Congress and the Congreso Nacional de Cirugía. Analysis of the #ACSCC20 and #CNCirugia2020

Objetivo El objetivo de este estudio es analizar el impacto de los congresos del American College of Surgeons Clinical Congress (ACSCC2020) y del Congreso Nacional de Cirugía de la Asociación Española de Cirujanos (CNC2020) en formato virtual por la pandemia SARS-CoV-2 según la huella digital. Material y métodos Se estudiaron los hashtags de Twitter #ACSCC20 y #CNCirugia2020 para determinar tuits, retuits, usuarios e impresiones. Se analizaron los datos sobre las cuentas con mayor influencia y la evolución histórica de los congresos entre 2015 y 2020. Utilizamos el software symplur para la recogida y análisis de los datos. Resultados Entre 2015 y 2017 hubo un incremento consistente en el número de tuits, participantes e impresiones. Entre 2018 y 2020, el ACS mantiene el número de impresiones con menor cantidad de tuits. Sin embargo, el CNC sigue creciendo y logra sus mejores métricas en el presente 2020. Encontramos diferencias estadísticamente significativas entre las cuentas más prolíficas del ACSCC frente al CNC (p<0,002), pero no existen diferencias entre las 10 cuentas más influyentes (p=0,19) o las cuentas con mayor número de impresiones (p=0,450). Conclusiones Los congresos virtuales generan un impacto global a través del uso de Twitter para la diseminación de conocimiento. En el presente 2020 el crecimiento del impacto en redes sociales ha sido proporcionalmente mayor en el CNC que en el ACSCC. No obstante, el congreso virtual del ACS generó mayor impacto en las redes sociales medido por el número de usuarios, tuits e impresiones entre 2015 y 2020 (AU)

Aim The objective of this study is to analyze the impact of the American College of Surgeons Clinical Congress (ACSCC2020) and the National Surgery Congress of the Spanish Association of Surgeons (CNC2020) in virtual format due to the SARS-CoV-2 pandemic according to the fingerprint.Material and methods The Twitter hashtags # ACSCC20 and # CNCirugia2020 were studied to determine tweets, retweets, users and impressions. The data on the accounts with the greatest influence and the historical evolution of the congresses between 2015 and 2020 were analyzed. We used the symplur software to collect and analyze the data. Results Between 2015 and 2017 there was a consistent increase in the number of tweets, participants and impressions. Between 2018 and 2020, the ACS maintains the number of impressions with the fewest number of tweets. However, the CNC continues to grow and achieves its best metrics in 2020. We found statistically significant differences between the most prolific accounts of the ACSCC versus the CNC (P<.002) but there are no differences between the 10 most influential accounts (P=.19) or the accounts with the highest number of impressions (P=.450). Conclusions Virtual congresses generate a global impact through the use of Twitter for the dissemination of knowledge. In the present 2020, the growth of the impact on social networks has been proportionally greater in the CNC than in the ACSCC. However, the ACS virtual congress generated the greatest impact on social networks measured by the number of users, tweets and impressions between 2015 and 2020 (AU)

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.

Association of Dry Eye with Laryngopharyngeal Reflux in Clinical Practice.

BACKGROUND: Dry eye disease (DED) is a common disorder, accounting for up to 35% of the general population. Therefore, we hypothesized that laryngopharyngeal reflux (LPR), inducing refluxate rising into airways, may involve the ocular surface and may either induce or worsen DED. AIM: To investigate the prevalence and relevance of suspected LPR in DED patients and subjects with refractive problems (RP) without DED, they were defined as non-dry eye group (NEG) in clinical practice. METHODS: This retrospective study included consecutive patients evaluated because of dry eye-like symptoms at eight tertiary ophthalmological clinics. Parameters included reflux symptom index (RSI), ocular surface disease index (OSDI), symptom assessment in dry eye (SANDE) for frequency and severity, Schirmer test, tear break-up time (BUT), and Oxford grading. RESULTS: The study included 245 subjects (72.5% females; mean age 56.3 years), 152 DED patients, and 93 sex- and age-matched NEG subjects. Pathological RSI (score>13) was detected in 80 subjects (32.6%); 68 (85%) with DED and 12 (15%) CG (OR = 8; p < .0001). In NEG, pathological RSI was associated with higher SANDE (Frequency and Severity), OSDI, and Schirmer scores (OR = 16.36; 14.51; 12.54; and 7.22, respectively. In DED patients, pathological RSI was associated with higher OSDI values (OR = 8.75). CONCLUSION: Patients with DED are at eight times higher risk for having pathological RSI than NEG patients. Moreover, pathological RSI was associated with more severe ocular symptoms both in DED and non-DED patients. The role of LPR in definite DED patients remains to be clarified, but this condition deserves to be investigated in managing patients with DED symptoms.

[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).

Cell-free DNA concentration and fragment size fraction correlate with FDG PET/CT-derived parameters in NSCLC patients.

PURPOSE: The aim of our study was to investigate the correlation between cfDNA concentration and fragment size fraction with FDG PET/CT- and CT-derived parameters in untreated NSCLC patient. METHODS: Fifty-three patients diagnosed of locally advanced or metastatic NSCLC who had undergone FDG PET/CT, CT and cfDNA analysis prior to any treatment were included in this retrospective study. CfDNA concentration was measured by fluorometry and fragment size fractions were determined by microchip electrophoresis. [18F]F-FDG PET/CT was performed and standardised uptake values (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated for primary, extrapulmonary and total disease. CT scans were evaluated according to RECIST 1.1 criteria. RESULTS: CfDNA concentration showed a positive correlation with extrapulmonary MTV (r2 = 0.36, P = 0.009), and extrapulmonary TLG (r2 = 0.35, P = 0.009) and their whole-body (wb) ratios. Higher concentrations of total cfDNA were found in patients with liver lesions. Short fragments of cfDNA (100-250 bp) showed a positive correlation with extrapulmonary MTV (r2 = 0.49, P = 0.0005) and extrapulmonary TLG (r2 = 0.39, P = 0.006) and their respective wb ratios, and a negative correlation with SUVmean (r2 = -0.31, P = 0.03) and SUVmean/SUVmax ratio (r2 = -0.34, P = 0.02). A higher fraction of short cfDNA fragments was found in patients with liver and pleural lesions. CONCLUSIONS: This study supports the hypothesis that cfDNA concentration and short cfDNA fragment size fraction reflect the tumour burden as well as metabolic activity in advanced NSCLC patients. This suggests their suitability as complementary tests for a more accurate diagnosis of tumour metabolic behaviour and to allow personalised therapies.

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.