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 11.14.2 (4.8-22.8) months, the mean ICT was 2.5 +/- 1.1 (1.0-4.0) months, the mean mPRGF AT was 12.4 +/- 2.0 (10.0-16.0) days, and for the global HTED the mean was 2.9 +/- 1.2 (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) 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.This study received funding from the Ministry of Economy and Competitiveness of the Spanish Government, within the project denominated SURFEYE (reference RTC-2014-2375-1)

Topical Tacrolimus for Corneal Subepithelial Infiltrates Secondary to Adenoviral Keratoconjunctivitis

Purpose: The objective of this study was to determine the efficacy and safety of topical tacrolimus compounded in the Pharmacy Service for the treatment of subepithelial corneal infiltrates (SEIs) secondary to adenoviral keratoconjunctivitis. Methods: This retrospective study included patients who had been dispensed topical tacrolimus for the treatment of SEIs during the previous year. Patients were treated with tacrolimus 0.03% eye drops twice daily or tacrolimus 0.02% ointment once daily. The following data were recorded: length of treatment, visual acuity before and after treatment, intraocular pressure before, during, and at the end of treatment, previous treatments, and the presence of SEIs after treatment. The subjective symptoms of the patients were also assessed. Results: Fifty-five patients (85 eyes) were included, 54.5% with bilateral involvement. A total of 31 (36.5%) eyes were treated with tacrolimus ointment and 54 eyes (63.5%) with tacrolimus eye drops. The median length of treatment was 185 days (p25–75: 93.5–426), and the mean follow-up duration was 363 days (p25–75: 148–540). In 62.35% of the eyes, the SEIs were reduced in number and size, and in 31.76%, they were eliminated. The patients had better visual acuity after treatment with highly statistically significant differences. Tolerance was good overall, being better in the eye drops group. Conclusions: Topical tacrolimus, compounded in the pharmacy, seems to be an effective and safe alternative for the treatment of SEIs secondary to adenovirus keratoconjunctivitis

Plasma Rich in Growth Factors membrane in the treatment of Limbal Stem Cell Deficiency

Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) (2019. Vancourver, Canada

Mini Cleanroom for the Manufacture of Advanced Therapy Medicinal Products (ATMP): Bioengineered Corneal Epithelium

Among several requirements for the manufacture of Advanced Therapy Medicinal Products (ATMP) are: following the guidelines of a pharmaceutical quality system, complying with Good Manufacturing Practice (GMP) and access to a cleanroom fulfilling strict environmental conditions (Class A work area and Class B environment). This makes ATMP expensive. Moreover, the production of many of these therapeutic products may also be unprofitable, as in most cases their use is limited to a few patients and to a single batch per manufacturing unit. To reduce costs, ATMP may be produced in a scaled-down system isolated from the external environment (isolator), allowing for placement of this facility in a Class D environment, which is much more permissive and less costly. In this work, we confirm that it is possible to manufacture bioengineered corneal epithelium inside an isolator while fulfilling all the safety assurance standards at an affordable cost for patients. This small-scale ultra-clean working environment complies with GMP guidelines and could be a solution for the high costs associated with conventional cleanroom ATMP production

A Simple, Safe, and Effective Method for Preparing Autologous Bio-Based Fibrin Glue for Ophthalmic Use

This study proposes a method to prepare autologous bio-based fibrin glue (FG) for use in ophthalmic surgery. FGs containing three fibrinogen concentrations and a thrombin concentrate were prepared using human blood from five donors (FG1: physiological fibrinogen concentration; FG2 and FG3: concentrated fibrinogen). The adhesion strength was tested, and the clinical safety and efficacy were studied in rabbit eyes in conjunctival surgery. A commercial FG was used as a control. From each donor, 2 mL of FG was prepared, containing 1 mL of 3.49 ± 0.78 (FG1), 17.74 ± 4.66 (FG2), or 47.46 ± 9.36 mg/mL (FG3) of fibrinogen and 1 mL of 2248.12 ± 604.20 UI/mL of thrombin. The average adhesion strength increased with the fibrinogen concentration, from 1.49 ± 0.39 kPa (FG1) to 3.14 ± 1.09 kPa (FG3). FG1 showed poor results when used for autograft adhesion. In contrast, the conjunctival autografts were successfully grafted using FG2 and FG3, revealing equivalent adhesion properties compared with commercial FG, but with less inflammation. In conclusion, FGs could be prepared on demand within minutes from small volumes of human blood, using a method that results in FGs which exhibit good adhesion capacity and are also safe and effective in a preclinical study

Hospital Pharmacy Compounding against COVID-19 pandemic

As in other areas of the health system, COVID-19 has had a dramatic impact on hospital compounding. This area has faced numerous challenges, including the shortage of frequent-use products (hydroalcoholic solutions, lopinavir/ritonavir suspension), the use of new preparations for SARS-CoV-2 (tocilizumab, remdesivir), or requests from overwhelmed wards unable to assume the safe preparation of a high volume of medications (intravenous solutions). The demand for all types of preparations (topic and oral medications, intravenous solutions) has increased dramatically. This increase has highlighted the shortage of resources allocated to this area, which has made it difficult to meet the high demand for preparations. In addition, the pandemic has revealed the scarcity of research on such basic aspects as agent stability and drug compatibility. One of the most relevant conclusions drawn from the COVID-19 pandemic is that the basic areas of hospital pharmacy, along with other, must be maintained and reinforced, as these are the areas that make us essential.YesComo todo el sector sanitario, la farmacotecnia hospitalaria ha sufrido el impacto de la pandemia de la COVID-19, enfrentándose a la necesidad de cubrir el desabastecimiento de productos de uso frecuente (soluciones hidroalcohólicas, lopinavir/ritonavir suspensión), a nuevas preparaciones surgidas de las nuevas necesidades provocadas por el SARS-CoV-2 (tocilizumab, remdesivir), o a peticiones de plantas desbordadas por la carga asistencial, incapaces de asumir con un mínimo de seguridad la preparación de numerosos medicamentos (mezclas intravenosas). El incremento de actividad ha sido en todo tipo de preparados (tópicos, orales y mezclas intravenosas) y ha puesto de manifiesto la escasez de recursos destinados a esta área, que se ha traducido en serios problemas para afrontar todas las elaboraciones necesarias, así como la falta de investigación en aspectos tan básicos como la estabilidad o la compatibilidad de medicamentos. Probablemente, una de las conclusiones más importantes que podemos extraer tras la COVID-19 es que —sin menospreciar otras áreas de la farmacia hospitalaria que también deben desarrollarse— debemos mantener y potenciar las áreas básicas de nuestra profesión. Aquellas que nos hacen imprescindibles

QobuR – A new in vitro human corneal epithelial model for preclinical drug screening

A new in vitro human corneal epithelial model (QobuR) obtained from normal limbal tissue has been developed to study ocular irritancy of different ophthalmic compounded drugs. Phenotypical characterization and transepithelial electrical resistance (TEER) of QobuR revealed essential similarities compared with a native human cornea, displaying functional markers and TEER values near 1500 Ωcm2 at day 7th of cellular differentiation. Using this model, ocular irritancy and barrier integrity alterations were evaluated using MTT reaction and variations in TEER. We found that some of the Non-Irritant products evaluated still damage the corneal epithelial integrity and current protocols for ocular irritancy should therefore include a barrier integrity evaluation. Moreover, in order to comprehensively evaluate corneal permeability of the active ingredients, we propose the use of QobuR as an all-in-one alternative method for evaluating ocular irritancy, barrier disruptions and permeability rates of topically applied ocular drugs to improve current in vitro drug testing procedures

Fibrin-Plasma Rich in Growth Factors Membrane for the Treatment of a Rabbit Alkali-Burn Lesion

Abstract: The purpose of this work is to describe the use of Fibrin-Plasma Rich in Growth Factors (PRGF) membranes for the treatment of a rabbit alkali-burn lesion. For this purpose, an alkali-burn lesion was induced in 15 rabbits. A week later, clinical events were evaluated and rabbits were divided into five treatment groups: rabbits treated with medical treatment, with a fibrin-PRGF membrane cultured with autologous or heterologous rabbit Limbal Epithelial Progenitor Cells (LEPCs), with a fibrin-PRGF membrane in a Simple Limbal Epithelial Transplantation and with a fibrin-PRGF membrane without cultured LEPCs. After 40 days of follow-up, corneas were subjected to histochemical examination and immunostaining against corneal or conjunctival markers. Seven days after alkali-burn lesion, it was observed that rabbits showed opaque cornea, new blood vessels across the limbus penetrating the cornea and epithelial defects. At the end of the follow-up period, an improvement of the clinical parameters analyzed was observed in transplanted rabbits. However, only rabbits transplanted with cultured LEPCs were positive for corneal markers. Otherwise, rabbits in the other three groups showed positive staining against conjunctival markers. In conclusion, fibrin-PRGF membrane improved the chemically induced lesions. Nonetheless, only fibrin-PRGF membranes cultured with rabbit LEPCs were able to restore the corneal surface