Pharmacological treatments for the correction of presbyopia.

Presbyopia affects between 1.7 and 2 billion people worldwide. Presbyopia significantly impacts productivity and quality of life in both developed and developing countries. During accommodation, the human eye changes its dioptric power by altering the shape of the lens, but the exact nature of this change has not been fully explained. Recently, topical treatments have been marketed for the treatment of presbyopia and others are under investigation. In order to prepare a review of these novel therapies, we searched the major biomedical search engines. We found 15 randomized clinical trials and 12 reviews that met our review criteria. There are two different strategies for this purpose, the pinhole effect that increases depth of focus and "crystalline lens relaxation" for which parasympathetic mimetics and lens oxidation intermediates have been used. The results are generally favorable in terms of improvement of near visual acuity, although the follow-up period of the studies is short. These are novel strategies in the early stages of research that could be useful in the treatment of presbyopia.

Afectación iatrogénica de la motilidad ocular por fármacos antitumorales inhibidores de los puntos de control / Iatrogenic impairment of ocular motility by immune checkpoint inhibitors

Se encontraron 4 revisiones sistemáticas que incluían este tipo de iatrogenia ocular, así como numerosos reportes de casos aislados. Los efectos adversos reportados comprenden: paresias oculomotoras, neuropatía óptica, atrofia óptica, síndromes miasteniformes, pseudo-orbitopatía tiroidea, síndrome del ápex orbitario e hipofisitis. La mayoría se manejaron sin interrupción o con interrupción parcial del tratamiento oncológico. Se requirieron tratamientos sistémicos agresivos para el manejo adecuado de la iatrogenia ocular.Es imprescindible que el oftalmólogo se familiarice con los nuevos tratamientos oncológicos ICI, capaces de provocar iatrogenia sobre la motilidad ocular grave e incapacitante para el paciente. La comunicación de efectos adversos con los tratamientos empleados puede ayudar al manejo más adecuado de estos pacientes. La investigación debe ir orientada al diagnóstico diferencial complejo y a optimizar las decisiones sobre los tratamientos oncológicos. (AU)

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile.We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events.It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments. (AU)

Iatrogenic affectation of ocular motility by immune checkpoint inhibitors.

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile. We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events. It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments.

Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

Entrenamiento quirúrgico con fantomas en cirugía de estrabismo / Surgical training with phantoms in strabismus surgery

Antecedentes y objetivo La simulación en el aprendizaje quirúrgico responde a necesidades éticas y pragmáticas. Nuestro propósito es describir los efectos sobre las habilidades quirúrgicas de la realización de un taller de entrenamiento quirúrgico en cirugía de estrabismo con fantomas. La preocupación por la seguridad del paciente obliga a plantearse el empleo de simuladores (virtuales y físicos tridimensionales) y modelos animales permite al aspirante practicar sin riesgos los procedimientos antes de enfrentarse a un caso real. Material y métodos Realización de un taller con contenido teórico previo y práctica real con fantomas diseñados para simular cirugía de estrabismo (globo ocular, 6 músculos, conjuntiva, párpado y cápsula de Tenon insertados en cráneo) de dimensiones anatómicas reales. Encuesta de satisfacción y evaluación subjetiva de aprendizaje por parte del alumno y del tutor experto según el modelo de evaluación de Kirkpatrick. Resultados Completaron la encuesta 100% de los 26 alumnos asistentes a dos cursos (15 alumnos en un curso y 11 alumnos en otro curso) y 100% de los tres tutores que participaron en ambos cursos; 20 eran médicos residentes y 20 especialistas en oftalmología. La satisfacción global de los alumnos fue de 8,2 (± 0,68). Conclusiones Según los resultados de la encuesta de evaluación de acciones formativas de Kirkpatrick, la percepción de alumnos y tutores es que el entrenamiento con fantomas en cirugía de estrabismo puede ayudar a mejorar las habilidades necesarias para una práctica segura e independiente. Siendo el objetivo último mejorar la seguridad del paciente (AU)

Background and purpose Simulation in surgical learning responds to ethical and pragmatic needs. Our purpose is to describe the effects on surgical skills of conducting a surgical training workshop on strabismus surgery with phantoms. Concern for patient safety makes it necessary to consider the use of simulators (virtual and three-dimensional physical) and animal models that allow the applicant to safely practice the procedures before facing a real case. Material and methods Realization of a workshop with previous theoretical content and real practice with phantoms designed to simulate strabismus surgery (eyeball, six muscles, conjunctiva, eyelid and Tenon capsule inserted in the skull) of real anatomical dimensions. Satisfaction survey and subjective evaluation of learning by the student and the expert tutor according to the Kirkpatrick evaluation model. Results 100% of the 26 students attending two courses (15 students in one course and 11 students in another course) and 100% of the three tutors who participated in both courses completed the survey. Twenty were resident doctors and 20 specialists in ophthalmology. The overall satisfaction of the students was 8.2 (± 0.68). Conclusions According to the results of the Kirkpatrick training actions evaluation survey, the perception of students and tutors is that training with phantoms in strabismus surgery can help improve the skills necessary for safe and independent practice. The ultimate goal being to improve patient safety (AU)

Surgical training with phantoms in strabismus surgery.

BACKGROUND AND PURPOSE: Simulation in surgical learning responds to ethical and pragmatic needs. Our purpose is to describe the effects on surgical skills of conducting a surgical training workshop on strabismus surgery with phantoms. Concern for patient safety makes it necessary to consider the use of simulators (virtual and three-dimensional physical) and animal models that allow the applicant to safely practice the procedures before facing a real case. MATERIAL AND METHODS: Realization of a workshop with previous theoretical content and real practice with phantoms designed to simulate strabismus surgery (eyeball, 6 muscles, conjunctiva, eyelid and tenon capsule inserted in the skull) of real anatomical dimensions. Satisfaction survey and subjective evaluation of learning by the student and the expert tutor according to the Kirkpatrick evaluation model. RESULTS: Total, 100% of the 26 students attending two courses (15 students in one course and 11 students in another course) and 100% of the 3 tutors who participated in both courses completed the survey. 20 were resident doctors and 20 specialists in ophthalmology. The overall satisfaction of the students was 8.2 (±0.68). CONCLUSIONS: According to the results of the Kirkpatrick training actions evaluation survey, the perception of students and tutors is that training with phantoms in strabismus surgery can help improve the skills necessary for safe and independent practice. The ultimate goal being to improve patient safety.

Corticodependent bilateral trochleitis.

Trochleitis is usually a transient and non-disabling inflammation of the trochlea of superior oblique. The case is presented of a difficult to manage bilateral trochleitis in a 29-year-old woman. After an exhaustive aetiological study with neuro-imaging tests, as well as an analysis of autoimmunity and infection, no underlying cause was found. Multiple injections of corticosteroids were required in both eyes, with a partial effect. Surgical intervention was finally decided in order to visually examine the trochlea, take biopsies, and inject methylprednisolone. These were effective in relieving the symptoms. This case is exceptional due to it involving both eyes and its severity, and represented a therapeutic challenge for the clinical team.

Poliuria en el adulto. Una aproximación diagnóstica basada en la fisiopatología / Polyuria in adults. A diagnostic approach based on pathophysiology

La poliuria es una condición clínica frecuente caracterizada por un volumen de orina inapropiadamente alto para los niveles de presión arterial y sodio plasmático del paciente (volumen de orina >3L/24h). Desde el punto de vista fisiopatológico se clasifica en 2 tipos: debido a una mayor excreción de solutos (osmolaridad urinaria >300mOsm/L) o debido a una incapacidad de aumentar la concentración de solutos (osmolaridad urinaria <150mOsm/L). En ocasiones pueden coexistir ambos mecanismos (osmolaridad urinaria 150-300mOsm/L). La poliuria supone un reto diagnóstico y su tratamiento correcto exige una evaluación de la historia clínica, la determinación de la osmolaridad urinaria, la estimación del aclaramiento de agua libre, el uso de pruebas de deprivación hídrica en la poliuria acuosa y la medición de electrólitos en sangre y orina en el caso de la poliuria osmótica (AU)

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 liters in 24 hours) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria (AU)

Antimicrobial cotton gauzes modified with poly(acrylic acid-co-maltodextrin) hydrogel using chitosan as crosslinker.

Cotton gauzes were grafted with a hydrogel of maltodextrin (MD) and poly(acrylic acid) (PAAc) using N-maleyl chitosan as crosslinker to obtain materials with antimicrobial properties. Reaction parameters including monomer, crosslinker, and initiator concentrations were studied. The modification with the copolymer poly(acrylic acid)-co-maltodextrin (PAAc-co-MD) was corroborated by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The grafted gauzes (gauze-g-(PAAc-co-MD)) were able to load vancomycin and inhibit the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. In addition, the incorporation of chitosan as crosslinker showed a synergistic effect against these bacteria. The prepared gauze-g-(PAAc-co-MD) materials could be used in the biomedical area particularly as antimicrobial wound dressings.

Polyuria in adults. A diagnostic approach based on pathophysiology.

Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 L in 24 h) for the patient's blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150-300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria.

Systemic bevacizumab as adjuvant therapy for recurrent respiratory papillomatosis in children: A series of three pediatric cases and literature review.

Recurrent respiratory papillomatosis (RRP), a viral disease caused by human papillomavirus (HPV), is the most common benign neoplasm of the larynx among children and the second most frequent cause of infantile hoarseness. The course of the disease is variable; some patients experience spontaneous remission, while others may develop an aggressive respiratory compromise. Especially juvenile-onset RRP cases experience shorter intervals between surgical interventions and thus more surgeries overall, causing high rates of depression and voice-related quality of life. Various local adjuvant therapies have been studied with mixed efficacy and some early potential but have failed to show consistent effect across large cohorts of patients. Bevacizumab, a recombinant monoclonal antibody that inhibits VEGF, has shown efficacy in patients with rapid regrowth of papillomas with severe airway compromise, and/or distal multisite spread of disease. We present three juvenile-onset RRP cases successfully managed with systemically administered bevacizumab.

Corticodependent bilateral trochleitis. / Trocleítis bilateral corticodependiente.

Trochleitis is usually a transient and non-disabling inflammation of the trochlea of superior oblique. The case is presented of a difficult to manage bilateral trochleitis in a 29-year-old woman. After an exhaustive aetiological study with neuro-imaging tests, as well as an analysis of autoimmunity and infection, no underlying cause was found. Multiple injections of corticosteroids were required in both eyes, with a partial effect. Surgical intervention was finally decided in order to visually examine the trochlea, take biopsies, and inject methylprednisolone. These were effective in relieving the symptoms. This case is exceptional due to it involving both eyes and its severity, and represented a therapeutic challenge for the clinical team.

Parálisis de sexto nervio craneal en adulto inmunocompetente con varicela / Sixth cranial nerve palsy in an immunocompetent adult patient with varicella

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Membrana amniótica en el tratamiento quirúrgico de diplopía posblefaroplastia / Amniotic membrane in the surgical treatment of post-blepharoplasty diplopia

Presentamos 2 casos consecutivos de diplopía vertical tras cirugía de blefaroplastia. Se trata de 2 mujeres de 41 y 63 años que presentaron diplopía binocular vertical tras blefaroplastia inferior bilateral con abordaje transconjuntival. La diplopía se presentó en ambos casos en el postoperatorio inmediato, siendo en uno de los casos estable y en otro progresiva. Con la sospecha de estrabismo restrictivo se planteó explorar los músculos extraoculares afectados, eliminar las adherencias y recubrimiento de los vientres musculares con membrana amniótica. La diplopía posblefaroplastia es una complicación infrecuente, pero muy grave, dadas las expectativas de estos pacientes. La literatura describe, hasta la fecha, resultados poco satisfactorios en su manejo. Consideramos que el recubrimiento muscular con membrana amniótica puede aportar mejores resultados en el manejo quirúrgico de estos pacientes, debido a su efecto antiinflamatorio y antiadherencial

Two consecutive cases are presented of vertical diplopia after blepharoplasty. They concern two women aged 41 and 63 years with vertical binocular diplopia after bilateral lower blepharoplasty using a trans-conjunctival approach. The diplopia was presented in both cases in the immediate postoperative period, being stable in one of the cases and progressive in the other. With the suspicion of restrictive strabismus, it was decided to explore the affected extra-ocular muscles, eliminate adhesions and coat the muscular bellies with amniotic membrane. Post-blepharoplasty diplopia is an uncommon, but very serious complication, given the expectations of these patients. The current literature reports unsatisfactory results in its management. In this study, it is considered that the muscular covering with amniotic membrane can provide better results in the surgical management of these patients, due to its anti-inflammatory and anti-adherence effect

Amniotic membrane in the surgical treatment of post-blepharoplasty diplopia. / Membrana amniótica en el tratamiento quirúrgico de diplopía posblefaroplastia.

Two consecutive cases are presented of vertical diplopia after blepharoplasty. They concern two women aged 41 and 63 years with vertical binocular diplopia after bilateral lower blepharoplasty using a trans-conjunctival approach. The diplopia was presented in both cases in the immediate postoperative period, being stable in one of the cases and progressive in the other. With the suspicion of restrictive strabismus, it was decided to explore the affected extra-ocular muscles, eliminate adhesions and coat the muscular bellies with amniotic membrane. Post-blepharoplasty diplopia is an uncommon, but very serious complication, given the expectations of these patients. The current literature reports unsatisfactory results in its management. In this study, it is considered that the muscular covering with amniotic membrane can provide better results in the surgical management of these patients, due to its anti-inflammatory and anti-adherence effect.

Preparation of Peppermint Oil-Based Nanodevices Loaded with Paclitaxel: Cytotoxic and Apoptosis Studies in HeLa Cells.

In this work, several normal, oil-in-water (o/w) microemulsions (MEs) were prepared using peppermint essential oil, jojoba oil, trans-anethole, and vitamin E as oil phases to test their capacity to load paclitaxel (PTX). Initially, pseudo-ternary partial phase diagrams were constructed in order to find the normal microemulsion region using d-α-tocopherol polyethylene glycol 1000 succinate (TPGS-1000) as surfactant and isobutanol (iso-BuOH) as co-surfactant. Selected ME formulations were loaded with PTX reaching concentrations of 0.6 mg mL-1 for the peppermint oil and trans-anethole MEs, while for the vitamin E and jojoba oil MEs, the maximum concentration was 0.3 mg mL-1. The PTX-loaded MEs were stable according to the results of heating-cooling cycles and mechanical force (centrifugation) test. Particularly, drug release profile for the PTX-loaded peppermint oil ME (MEPP) showed that ∼ 90% of drug was released in the first 48 h. Also, MEPP formulation showed 70% and 90% viability reduction on human cervical cancer (HeLa) cells after 24 and 48 h of exposure, respectively. In addition, HeLa cell apoptosis was confirmed by measuring caspase activity and DNA fragmentation. Results showed that the MEPP sample presented a major pro-apoptotic capability by comparing with the unloaded PTX ME sample.

Immobilization of antimicrobial and anti-quorum sensing enzymes onto GMA-grafted poly(vinyl chloride) catheters.

Catheter-associated infections still represent a challenging thread because of the likelihood of biofilm formation. The aim of this work was the surface modification of catheters to immobilize lysozyme and acylase under mild conditions while preserving antimicrobial and anti-quorum sensing performances. Glycidyl methacrylate (GMA) was grafted onto poly(vinyl chloride) (PVC) catheters by a pre-irradiation method. The effects of monomer concentration, pre-irradiation dose, reaction time, monomer concentration and reaction temperature were investigated. The grafting process was monitored using FTIR-ATR spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and swelling data. Lysozyme was directly immobilized onto PVC-g-GMA maintaining the hydrolytic activity, which hindered Staphylococcus aureus adhesion. For acylase immobilization, the PVC-g-GMA catheters were reacted with ethylenediamine and glutaraldehyde in order to facilitate acylase covalent binding. Free acylase in solution demonstrated notably capability to act as quorum sensing inhibitor, as observed using Chromobacterium violaceum as biosensor, by degrading a wide variety of acylated homoserine lactones (AHLs), including those produced by Pseudomonas aeruginosa and Acinetobacter baumannii. Acylase-immobilized PVC-g-GMA catheters were challenged against degradation of AHLs and the activity monitored using both the biosensor and HPLC-MS. Relevantly, the functionalized catheters completely degraded all tested AHL signals, opening new ways of preventing biofilm formation on medical devices.

Poly(methacrylic acid)-modified medical cotton gauzes with antimicrobial and drug delivery properties for their use as wound dressings.

Medical cotton gauzes were modified by grafting poly(methacrylic acid) (PMAA) via free radical polymerization to obtain wound dressings with antimicrobial and drug delivery properties. The effect of several reaction parameters including monomer and initiator concentrations, reaction time, and temperature was studied. The grafting was confirmed by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), swelling studies, and scanning electron microscopy (SEM). The grafted cotton gauzes (gauze-g-PMAA) samples were loaded with ZnO nanoparticles to endow with antibacterial properties. Also, they were tested as drug eluting systems using nalidixic acid as antimicrobial agent. The antibacterial activity of the ZnO-loaded gauze-g-PMAA samples was evaluated against Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis). The PMAA-grafted gauzes showed antibacterial activity and inhibited the growth of both microorganisms. These results suggest that the PMAA-grafted cotton gauzes could be used in the biomedical area particularly as antimicrobial and drug-eluting wound dressings.

Spruce xylan/HEMA-SBA15 hybrid hydrogels as a potential scaffold for fibroblast growth and attachment.

A hybrid hydrogel (GHC-SBA15) based on spruce xylan (HC), 2-hydroxyethyl methacrylate (HEMA), and mesoporous silica (SBA15) was prepared with the intended use of fibroblast attachment and growth. Xylan was functionalized with acryloyl chloride to introduce vinyl groups and was crosslinked by radical polymerization with HEMA in presence of SBA15. Infrared spectroscopy and nuclear magnetic resonance confirmed the copolymerization of HEMA with xylan. Up to 20 wt.% addition, SBA15 was homogenously incorporated in the structured hydrogel network as observed by SEM. Moreover, nitrogen adsorption-desorption, small angle X-ray scattering and transmission electron microscopy indicated that the mesoporous SBA15 framework was maintained and that the hybrid hydrogel was a physical mixture of SBA15 with the copolymer HC/HEMA. Rheological analysis revealed that addition of 20% w/w SBA15 into hydrogel enhanced significantly the mechanical properties. In addition, we demonstrate that fibroblast L929 cells grew and spread on GHC-SBA15. Cell viability was within the expected range.