Assessing health outcomes: a systematic review of electronic patient-reported outcomes in oncology.

PURPOSE: This study investigates the clinical impact of electronic patient-reported outcome (ePRO) monitoring apps/web interfaces, aimed at symptom-management, in cancer patients undergoing outpatient systemic antineoplastic treatment. Additionally, it explores the advantages offered by these applications, including their functionalities and healthcare team-initiated follow-up programmes. METHODS: A systematic literature review was conducted using a predefined search strategy in MEDLINE. Inclusion criteria encompassed primary studies assessing symptom burden through at-home ePRO surveys in adult cancer patients receiving outpatient systemic antineoplastic treatment, whenever health outcomes were evaluated. Exclusion criteria excluded telemedicine-based interventions other than ePRO questionnaires and non-primary articles or study protocols. To evaluate the potential bias in the included studies, an exhaustive quality assessment was conducted, as an additional inclusion filter. RESULTS: Among 246 identified articles, 227 were excluded for non-compliance with inclusion/exclusion criteria. Of the remaining 19 articles, only eight met the rigorous validity assessment and were included for detailed examination and data extraction, presented in attached tables. CONCLUSION: This review provides compelling evidence of ePRO monitoring's positive clinical impact across diverse cancer settings, encompassing various cancer types, including early and metastatic stages. These systems are crucial in enabling timely interventions and reducing communication barriers, among other functionalities. While areas for future ePRO innovation are identified, the primary limitation lies in comparing clinical outcomes of reviewed articles, due to scale variability and study population heterogeneity. To conclude, our results reaffirm the transformative potential of ePRO apps in oncology and their pivotal role in shaping the future of cancer care.

Robotic chemotherapy compounding: A multicenter productivity approach.

INTRODUCTION: The aim of this study is to compare productivity of the KIRO Oncology compounding robot in three hospital pharmacy departments and identify the key factors to predict and optimize automatic compounding time. METHODS: The study was conducted in three hospitals. Each hospital compounding workload and workflow were analyzed. Data from the robotic compounding cycles from August 2017 to July 2018 were retrospectively obtained. Nine cycle specific parameters and five productivity indicators were analysed in each site. One-to-one differences between hospitals were evaluated. Next, a correlation analysis between cycle specific factors and productivity indicators was conducted; the factors presenting a highest correlation to automatic compounding time were used to develop a multiple regression model (afterwards validated) to predict the automatic compounding time. RESULTS: A total of 2795 cycles (16367 preparations) were analysed. Automatic compounding time showed a relevant positive correlation (ǀrs|>0.40) with the number of preparations, number of vials and total volume per cycle. Therefore, these cycle specific parameters were chosen as independent variables for the mathematical model. Considering cycles lasting 40 minutes or less, predictability of the model was high for all three hospitals (R2:0.81; 0.79; 0.72). CONCLUSION: Workflow differences have a remarkable incidence in the global productivity of the automated process. Total volume dosed for all preparations in a cycle is one of the variables with greater influence in automatic compounding time. Algorithms to predict automatic compounding time can be useful to help users in order to plan the cycles launched in KIRO Oncology.

Validación galénica del colirio de plasma rico en factores de crecimiento / Galenic validation of plasma rich in growth factors eye drops

Objetivo: Evaluación galénica del proceso de obtención y almacenamiento del colirio de plasma rico en factores de crecimiento PRGF-Endoret(R). Método: Para evaluar la asepsia en la obtención del colirio de PRGFEndoret(R) se realizó un ensayo de esterilidad siguiendo las normas descritas en la Farmacopea Europea y se analizó la estanqueidad de los dispensadores de colirio de PRGF-Endoret(R). Asimismo, se estudiaron las propiedades químicas y biológicas del colirio tras su proceso de obtención y almacenamiento. Se incluyeron ensayos de filtración del colirio, de un ciclo de congelación a -20 ºC y descongelación, así como de estabilidad durante tres y seis meses almacenados a -20 ºC. Resultados: Los ensayos de esterilidad mostraron que no hubo crecimiento microbiano en ninguno de los dispensadores analizados y se observó que el 100% de los monodosis analizados y el 98,4% de los tapones mantenían el hermetismo. Todos los factores de crecimiento analizados permanecieron constantes tras el filtrado del colirio de PRGF-Endoret(R). Además, todos los estudios de estabilidad llevados a cabo con el colirio de PRGF-Endoret(R) en el presente estudio mostraron que no se produjeron cambios significativos en los niveles de factores de crecimiento, en la actividad proliferativa celular ni en las características químicas analizadas. Conclusiones: El presente trabajo muestra que el proceso de elaboración del colirio de PRGF-Endoret(R) se lleva a cabo de forma controlada, aséptica y segura, siguiendo las normas descritas en la Farmacopea Europea. Además, el colirio de PRGF-Endoret(R) obtenido mantiene sus propiedades físico-químicas y biológicas tras someterlo a diferentes tiempos y temperaturas de almacenamiento

Objective: Galenic evaluation of the process for obtaining and storing the platelet rich in growth factors PRGF-Endoret(R) eye drops. Method: To assess whether the PRGF-Endoret(R) eye drops process is aseptically obtained, a sterility test was carried out on the eye drops; the tightness of the PRGF-Endoret(R) eye drops containers was also analyzed. Likewise, the chemical and biological properties of the PRGF-Endoret(R) eye drops were evaluated after the obtaining process and storage. Eye drop filtration tests, one cycle of freezing at -20 °C and thawing, and eye drop stability for three and six months stored at -20 °C were included. Results: The results obtained in the sterility test showed no microbial contamination in any of the analyzed eyedropper; tightness test showed that 100% of the eyedrop containers and the 98.4% of the plugs analyzed remained hermetic. On the other hand, all the growth factors measured remained constant after filtering the PRGF-Endoret(R) eye drops. Furthermore, the different eye drop stability tests carried out in this study showed no significant changes in the growth factors levels, cell proliferative activity or in the chemical characteristics analyzed. Conclusions: The PRGF-Endoret(R) eye drops are obtained in a safety and aseptic manner following the guidelines issued by the Spanish Agency for Drugs and Health Products and the Ministry of Health to obtain medicines for human use. The PRGF-Endoret(R) eye drops maintain their physical-chemical and biological properties after being subjected to different storage times and temperatures

Galenic validation of plasma rich in growth factors eye drops.

OBJECTIVE: Galenic evaluation of the process for obtaining and storing the platelet rich in growth factors PRGF-Endoret® eye drops. METHOD: To assess whether the PRGF-Endoret® eye drops process is aseptically obtained, a sterility test was carried out on the eye drops; the tightness of the PRGF-Endoret® eye drops containers was also analyzed. Likewise, the chemical and biological properties of the PRGF- Endoret® eye drops were evaluated after the obtaining process and storage.  Eye drop filtration tests, one cycle of freezing at -20 °C and thawing, and  eye drop stability for three and six months stored at -20 °C were included. RESULTS: The results obtained in the sterility test showed no microbial  contamination in any of the analyzed eyedropper; tightness test showed that  100% of the eyedrop containers and the 98.4% of the plugs analyzed  remained hermetic. On the other hand, all the growth factors measured  remained constant after filtering the PRGF-Endoret® eye drops.  Furthermore, the different eye drop stability tests carried out in this study  showed no significant changes in the growth factors levels, cell proliferative  activity or in the chemical characteristics analyzed. Conclusions: The PRGF-Endoret® eye drops are obtained in a safety and aseptic manner following the guidelines issued by the Spanish Agency  for Drugs and Health Products and the Ministry of Health to obtain medicines for human use. The PRGF-Endoret® eye drops maintain their physical-chemical and biological properties after being subjected to different  storage times and temperatures.

Objetivo: Evaluación galénica del proceso de obtención y almacenamiento del colirio de plasma rico en factores de crecimiento PRGF- Endoret®. Método: Para evaluar la asepsia en la obtención del colirio de PRGFEndoret ® se realizó un ensayo de esterilidad siguiendo las normas  descritas en la Farmacopea Europea y se analizó la estanqueidad de los dispensadores de colirio de PRGF-Endoret®. Asimismo, se estudiaron las propiedades químicas y biológicas del colirio tras su proceso de obtención y almacenamiento. Se incluyeron ensayos de filtración del colirio,  de un ciclo de congelación a ­20 ºC y descongelación, así como de  estabilidad durante tres y seis meses almacenados a ­20 ºC.Resultados: Los ensayos de esterilidad mostraron que no hubo crecimiento microbiano en ninguno de los dispensadores analizados y se  observó que el 100% de los monodosis analizados y el 98,4% de los tapones mantenían el hermetismo. Todos los factores de crecimiento  analizados permanecieron constantes tras el filtrado del colirio de PRGF- Endoret®. Además, todos los estudios de estabilidad llevados a cabo con el  colirio de PRGF-Endoret® en el presente estudio mostraron que no se  produjeron cambios significativos en los niveles de factores de crecimiento,  en la actividad proliferativa celular ni en las características químicas  analizadas.Conclusiones: El presente trabajo muestra que el proceso de elaboración del colirio de PRGF-Endoret® se lleva a cabo de forma  controlada, aséptica y segura, siguiendo las normas descritas en la  farmacopea Europea. Además, el colirio de PRGF-Endoret® obtenido  mantiene sus propiedades físico-químicas y biológicas tras someterlo a  diferentes tiempos y temperaturas de almacenamiento.

Plasma rich in growth factors membrane as coadjuvant treatment in the surgery of ocular surface disorders.

To evaluate the safety and efficacy of the surgical use of plasma rich in growth factors fibrin membrane (mPRGF) in different ocular surface pathologies.Fifteen patients with different corneal and conjunctival diseases were included in the study. Patients were grouped according to the use of mPRGF as graft (corneal and/or conjunctival) or dressing; they were also grouped according to the surgical subgroup of intervention (persistent corneal ulcer [PCU], keratoplasty, superficial keratectomy, corneal perforation, and pterygium). Best corrected visual acuity, intraocular pressure (IOP), inflammation control time (ICT), mPRGF AT (PRGF membrane absorption time), and the healing time of the epithelial defect (HTED) were evaluated throughout the clinical follow-up time. Safety assessment was also performed reporting all adverse events.mPRGF showed a total closure of the defect in 13 of 15 patients (86.7%) and a partial closure in 2 patients (13.3%). The mean follow-up time was 11.1 ±â€Š4.2 (4.8-22.8) months, the mean ICT was 2.5 ±â€Š1.1 (1.0-4.0) months, the mean mPRGF AT was 12.4 ±â€Š2.0 (10.0-16.0) days, and for the global HTED the mean was 2.9 ±â€Š1.2 (1-4.8) months. Results showed an improvement in BCVA in all patients, with an overall improvement of 2.9 in Vision Lines. The BCVA significantly improved (P < .05) in the groups of corneal graft and dressing. In the PCU subgroup (6 patients), the healing time of epithelial defect was significantly reduced (P < .05) in patients treated only with the mPRGF in comparison to those which mPRGF therapy was associated to the amniotic membrane. The IOP remained stable (P > .05) throughout the clinical follow-up time. No adverse events were reported after mPRGF use.The mPRGF is effective and safe as coadjuvant treatment in surgeries related with ocular surface disorders, being an alternative to the use of amniotic membrane. The mPRGF accelerates tissue regeneration after ocular surface surgery thus minimizing inflammation and fibrosis.

Consenso SEO-SEFH sobre recomendaciones de utilización y elaboración de preparaciones oftálmicas / Consensus SEO-SEFH of recommendations for use and compounding of ophthalmic preparations

Son muchos los medicamentos que, aun habiendo demostrado eficacia y seguridad en diferentes indicaciones oftalmológicas, no están autorizados ni disponibles comercialmente en una forma adecuada para esta vía de administración. Esto implica, por un lado, que se deban utilizar según la legislación que regula la disponibilidad de medicamentos en situaciones especiales y, por otro, que se deban preparar en los Servicios de Farmacia para su administración por vía oftálmica, conforme a unos criterios de calidad que aseguren su efectividad, estabilidad y esterilidad. Este documento recoge un consenso entre la Sociedad Española de Oftalmología y la Sociedad Española de Farmacia Hospitalaria sobre aquellas preparaciones con suficiente evidencia respecto a su eficacia y seguridad para su uso no autorizado en indicaciones y vía de administración oftálmicas. Se incluyen recomendaciones para su utilización de acuerdo con la legislación vigente. Además, con el ánimo de armonizar la preparación de inyecciones intraoculares en los Servicios de Farmacia Hospitalaria, se establecen unas recomendaciones generales para su elaboración siguiendo los estándares establecidos en la Guía de Buenas Prácticas de Preparación de Medicamentos en los Servicios de Farmacia Hospitalaria. En estas recomendaciones se incluyen apartados como el lugar de preparación, el material, la técnica, el envasado, el periodo de validez, el control de calidad, la prescripción y la trazabilidad de las preparaciones intraoculares (AU)

There are many medicinal products that, although having shown efficacy and safety in different ophthalmological indications, they are not authorized or commercially available for ophthalmic administration. This implies, on one hand, that they must be used according to legislation that regulates the availability of medicines in special situations and, on the other hand, that they must be prepared in the pharmacy services for ophthalmic administration, according to quality criteria to ensure its effectiveness, stability and sterility. This document gathers the consensus between the Spanish Society of Ophthalmology and the Spanish Society of Hospital Pharmacy about these selected preparations which have shown enough evidence in their efficacy and safety for their ophthalmic use (off label) and ophthalmic administration. This document includes recommendations about its use according to the current legislation. In addition, with the aim of harmonizing the preparation of intraocular injections in the hospital pharmacy services, general recommendations are set in this document to ensure the compliance with standards established in the Spanish Guideline for Good Preparation Practices of Medicinal Products in Hospital Pharmacies. These recommendations include sections such as the area of preparation, material, technique, packaging, stability, quality control, prescription and traceability of intraocular preparations (AU)

Consensus SEO-SEFH of recommendations for use and compounding of ophthalmic preparations.

There are many medicinal products that, although having shown efficacy and  safety in different ophthalmological indications, they are not authorized or  commercially available for ophthalmic administration. This implies, on one hand,  that they must be used according to legislation that regulates the availability of  medicines in special situations and, on the other hand, that they must be  prepared in the pharmacy services for ophthalmic administration, according to  quality criteria to ensure its effectiveness, stability and sterility. This document  gathers the consensus between the Spanish Society of Ophthalmology and the  Spanish Society of Hospital Pharmacy about these selected preparations which  have shown enough evidence in their efficacy and safety for their ophthalmic use (off label) and ophthalmic administration. This document includes  recommendations about its use according to the current legislation. In addition,  with the aim of harmonizing the preparation of intraocular injections in the  hospital pharmacy services, general recommendations are set in this document  to ensure the compliance with standards established in the Spanish Guideline for Good Preparation Practices of Medicinal Products in Hospital Pharmacies. These  recommendations include sections such as the area of preparation, material,  technique, packaging, stability, quality control, prescription and traceability of  intraocular preparations.

Son muchos los medicamentos que, aun habiendo demostrado eficacia y seguridad en diferentes indicaciones oftalmológicas, no están autorizados ni disponibles comercialmente en una forma adecuada para esta vía de  administración.Esto implica, por un lado, que se deban utilizar según la legislación que regula la disponibilidad de medicamentos en situaciones especiales y, por otro, que se  deban preparar en los Servicios de Farmacia para su administración por vía  oftálmica, conforme a unos criterios de calidad que aseguren su efectividad,  estabilidad y esterilidad. Este documento recoge un consenso entre la Sociedad  Española de Oftalmología y la Sociedad Española de Farmacia Hospitalaria sobre  aquellas preparaciones con suficiente evidencia respecto a su eficacia y  seguridad para su uso no autorizado en indicaciones y vía de administración  oftálmicas. Se incluyen recomendaciones para su utilización de acuerdo con la  legislación vigente. Además, con el ánimo de armonizar la preparación de  inyecciones intraoculares en los Servicios de Farmacia Hospitalaria, se  establecen unas recomendaciones generales para su elaboración siguiendo los  estándares establecidos en la Guía de Buenas Prácticas de Preparación de  Medicamentos en los Servicios de Farmacia Hospitalaria. En estas  recomendaciones se incluyen apartados como el lugar de preparación, el  material, la técnica, el envasado, el periodo de validez, el control de calidad, la  prescripción y la trazabilidad de las preparaciones intraoculares.

¿Son complejos los pacientes atendidos por unidades de cuidados paliativos domiciliarias? / Are the patients attended by home care support teams complex?

No disponible

Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops.

PURPOSE: To provide preliminary data about efficacy and safety of plasma rich in growth factors (PRGF) eye-drops in neurotrophic keratitis (NK) and to analyze the possible influence of certain variables on treatment outcomes. METHODS: This retrospective study included patients with stages 2-3 of NK treated with PRGF eye-drops. Primary endpoint was the resolution time of corneal ulcer defect. Outcome measures including percentage of ulcer closure at 4 weeks, Ocular Surface Disease Index (OSDI), Best-Corrected Visual Acuity (BCVA) and Visual Analogue Scale (VAS) were also evaluated before and after treatment with PRGF. The influence of some patients' clinical variables on results was assessed. Safety assessment was also performed reporting all adverse events. RESULTS: Thirty-eight treated eyes in a total of thirty-one patients were evaluated, of which five cases had no prior response to autologous serum treatment. Most cases (97.4%) achieved the complete resolution of corneal defect/ulcer. Mean resolution time was 11.4 weeks (SD = 13.7). A statistical significant (p < 0.05) reduction in OSDI (60.9%), VAS frequency (59.9%), VAS severity (57.0%) and improvement in BCVA (52.8%) was observed. The results were stratified according to the pathology stage and to the identified potential effect modifiers variables. Only one adverse event was reported in one patient (2.6%). CONCLUSIONS: PRGF eye-drops could be a safe and effective therapeutic option for patients with stages 2-3 of NK, showing high rates of corneal defect/ulcer resolution in short times, either in reducing signs and symptoms of NK, and therefore preventing the progression of NK to greater ocular complications.

Silk Fibroin Films for Corneal Endothelial Regeneration: Transplant in a Rabbit Descemet Membrane Endothelial Keratoplasty.

Purpose: Develop a silk fibroin (SF)-based artificial endothelial graft for its use in a rabbit Descemet membrane endothelial keratoplasty (DMEK). Methods: Human and rabbit artificial corneal endothelial grafts were developed through the culture of human and rabbit corneal endothelial cells (CECs) on SF films. Rabbit artificial SF endothelial grafts were transplanted in a DMEK surgery into a rabbit in vivo model. Results: SF artificial endothelial grafts showed the characteristic endothelial markers: zonula occludens (ZO-1) and Na+/K+ ATPase. In a rabbit model of DMEK surgery, SF artificial endothelial graft restored the corneal transparency and thickness at 6 week of follow-up. Anterior segment optical coherence tomography revealed the SF graft as a fully integrated component in the corneal tissue, displaying a similar corneal thickness and endothelial cell count when compared with its healthy contralateral cornea. Histologic analysis showed that the SF artificial endothelial graft was attached and integrated on the surface of the corneal stroma without a significant inflammatory reaction, and rabbit CECs consisted in a monolayer that showed their characteristic markers ZO-1 and Na+/K+ ATPase, suggesting proper intercellular junctions and cellular pump function. Conclusions: We have developed SF films with biological properties that supported the growth of rabbit and human CECs, which showed normal morphology and characteristic markers; and with mechanical properties that allowed its use in a DMEK surgery, proving its in vivo functionality in a rabbit model of endothelial dysfunction.

The Effect of Immunologically Safe Plasma Rich in Growth Factor Eye Drops in Patients with Sjögren Syndrome.

PURPOSE: The objective was to provide preliminary information about the efficacy and safety of immunologically safe plasma rich in growth factor (immunosafe PRGF) eye drops in the treatment of moderate to severe dry eye in patients with primary and secondary Sjögren's syndrome (SS) and to analyze the influence of several variables on treatment outcomes. METHODS: This retrospective study included patients with SS. All patients were treated with previously immunosafe PRGF eye drops to reduce the immunologic component contents. Ocular Surface Disease Index (OSDI) scale, best-corrected visual acuity (BCVA), visual analog scale (VAS) frequency, and VAS severity outcome measures were evaluated before and after treatment with immunosafe PRGF. The potential influence of some patient clinical variables on results was also assessed. Safety assessment was also performed reporting all adverse events. RESULTS: Twenty-six patients (12 patients with primary SS, and 14 patients suffering secondary SS) with a total of 52 affected eyes were included and evaluated. Immunosafe PRGF treatment showed a significant reduction (P < 0.05) in OSDI scale (41.86%), in BCVA (62.97%), in VAS frequency (34.75%), and in VAS severity (41.50%). BCVA and VAS frequency scores improved significantly (P < 0.05) after concomitant treatment of PRGF with corticosteroids. Only 2 adverse events were reported in 2 patients (7.7% of patients). CONCLUSIONS: Signs and symptoms of dry eye syndrome in patients with SS were reduced after treatment with PRGF-Endoret eye drops. Immunosafe PRGF-Endoret is safe and effective for treating patients with primary and secondary SS.

Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model.

Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of endothelial dysfunction. This strategy could supply extra endothelial tissue and compensate the deficit of cadaveric grafts for corneal endothelial transplantation.

Polymeric nanocapsules: a potential new therapy for corneal wound healing.

Corneal injuries are one of the most frequently observed ocular diseases, leading to permanent damage and impaired vision if they are not treated properly. In this sense, adequate wound healing after injury is critical for keeping the integrity and structure of the cornea. The goal of this work was to assess the potential of polymeric nanocapsules, either unloaded or loaded with cyclosporine A or vitamin A, alone or in combination with mitomycin C, for the treatment of corneal injuries induced by photorefractive keratectomy surgery. The biopolymers selected for the formation of the nanocapsules were polyarginine and protamine, which are known for their penetration enhancement effect. The results showed that, following topical instillation to a mouse model of corneal injury, all the nanocapsule formulations, either unloaded or loaded with cyclosporine A or vitamin A, were able to stimulate corneal wound healing. In addition, the healing rate observed for the combination of unloaded protamine nanocapsules with mitomycin C was comparable to the one observed for the positive control Cacicol®, a biopolymer known as a corneal wound healing enhancer. Regarding the corneal opacity, the initial grade of corneal haze (>3) induced by the photorefractive keratectomy was more rapidly reduced in the case of the positive control, Cacicol®, than in corneas treated with the nanocapsules. In conclusion, this work shows that drug-free arginine-rich (polyarginine, protamine) nanocapsules exhibit a positive behavior with regard to their potential use for corneal wound healing.

Safety and Efficacy of Autologous Plasma Rich in Growth Factors Eye Drops for the Treatment of Evaporative Dry Eye.

PURPOSE: To provide preliminary information about the safety and efficacy of plasma rich in growth factors (PRGF) in the treatment of evaporative dry eye (EDE) and analyze the influence of certain variables on treatment outcomes. METHODS: This retrospective study included patients with EDE treated between January 2011 and December 2013. Outcome measures including signs and symptoms of the disease were evaluated before and after treatment. The influence of some of the patient's clinical variables on results was assessed. Safety assessment was also performed. RESULTS: Eighty-three patients with a total of 156 eyes were evaluated. Statistically significant reductions in the Ocular Surface Disease Index (38.2%), best-corrected visual acuity (27.4%), Visual Analogue Scale scores for frequency (32%) and severity (34%), and a significant improvement in the Schirmer test scores (177.5%) were observed (p < 0.05). The results were stratified according to the identified potential effect modifiers. Only four adverse events were reported. All of them were mild and resolved within a few days. CONCLUSIONS: Results suggest that PRGF eye drops could be a safe and effective treatment in reducing EDE signs and symptoms. When treating patients, the possible influence of some clinical variables must be taken into account.

Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease.

Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. Menthol (200 µM) first excited and then inactivated this augmented spontaneous and cold-evoked activity. Comparatively, corneal polymodal nociceptors of tear-deficient eyes remained silent and exhibited only a mild sensitization to acidic stimulation, whereas mechanonociceptors were not affected. Dryness-induced changes in peripheral cold thermoreceptor responsiveness developed in parallel with a progressive excitability enhancement of corneal cold trigeminal ganglion neurons, primarily due to an increase of sodium currents and a decrease of potassium currents. In corneal polymodal nociceptor neurons, sodium currents were enhanced whereas potassium currents remain unaltered. In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED.

Autologous Plasma Rich in Growth Factors Eyedrops in Refractory Cases of Ocular Surface Disorders.

PURPOSE: Preliminary information about the safety and efficacy of plasma rich in growth factors (PRGF) eyedrops in the treatment of refractory cases of diverse ocular surface disorders (OSDs) is presented here. MATERIAL AND METHODS: This retrospective cohort study included cases with OSDs refractory to previous treatment with conventional treatments or autologous serum or cyclosporine, and treated with PRGF eyedrops. The signs and symptoms of ocular surface disorders [using the ocular surface disease index (OSDI), best-corrected visual acuity (BCVA), visual analog scale (VAS) frequency and VAS severity] were evaluated before and after treatment with PRGF. A safety assessment was also performed reporting all adverse events or complications. RESULTS: Forty-one patients with a total of 80 treated eyes were evaluated. Statistically significant reductions in the OSDI scale (39.27%), VAS frequency (38.9%) and VAS severity (40.3%), and a significant improvement in BCVA (54.86%) were all observed (p < 0.05). The results were stratified according to the identified potential effect modifiers. There were only two adverse events (eye redness and eyelid inflammation), which were reported as mild and resolved in a few days. CONCLUSIONS: PRGF eyedrops could be a safe and effective treatment option for refractory cases of OSDs. When treating patients the possible influence on the results of some clinical variables must be taken into account.

Preservation of Biological Activity of Plasma and Platelet-Derived Eye Drops After Their Different Time and Temperature Conditions of Storage.

PURPOSE: To analyze whether plasma rich in growth factors (PRGF) eye drops preserve their biological characteristics and activity after storage for 3 and 6 months at -20°C, at 4°C, and at room temperature for 72 hours, compared with fresh samples (t0). METHODS: Blood from 6 healthy donors was harvested and centrifuged to obtain PRGF free of leukocytes. Resulting PRGF eye drops were stored for 3 and 6 months at -20°C. At each time, 2 aliquots were maintained at room temperature or at 4°C for 72 hours. Platelet-derived growth factor-AB, transforming growth factor-ß1, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor-1, angiopoietin-1, and thrombospondin-1 were quantified at each time and temperature of storage. Also, the effect of PRGF eye drops on proliferation of primary human keratocytes was evaluated. RESULTS: All the analyzed growth factor levels remained constant at each time and storage condition. No differences were observed in the proliferative activity of keratocytes after treatment with PRGF eye drops at any studied time or temperature. Finally, there was no microbial contamination in any of the PRGF eye drops. CONCLUSIONS: The preservation of the PRGF eye drops at -20°C for up to 3 and 6 months does not mean reduction of the main growth factors and proteins implicated in ocular surface wound healing. Eye drop characteristics and in vitro biological activity were not affected by their usage and conservation for 72 hours at 4°C or at room temperature.

Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies.

The use of blood derivatives represents an alternative therapeutic approach that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing. Autologous serum eye drops and platelet-enriched plasma eye drops are being used in the treatment of different ophthalmological disorders. In this review, we summarize the different blood-derived formulations used in the treatment and care of ocular surface disorders. The biological basis and use of autologous serum and plasma rich in growth factors are deeply evaluated as well as the challenges to be addressed in the future in this new generation of blood-derived therapies.