DEVELOPMENT OF A METHOD FOR CONSTRUCTING AND ASSESSING THE RELIABILITY OF HYPOTHESES ABOUT THE INTERRELATION OF A COMBINATION OF CYTOKINES AND OPHTHALMIC PREPARATIONS USING AN INTELLIGENT INFORMATION SYSTEM

В работе рассмотрено сравнение экспериментальных распределений количества клеток для определения цитологического и иммунологического эффекта, оказываемого одновременным воздействием офтальмологических препаратов Броксинак® и Офтальмоферон® на клетки с конъюнктивы больного человека, направленное на совершенствование методики оценки комбинаций офтальмологических лекарственных средств in vitro. Доклинические исследования дают возможность определить эффективность применения лекарственных средств, возможные противопоказания и побочные эффекты, чтобы в дальнейшем определиться с объемом клинических испытаний и самой возможностью их проведения. В последнее время в различных областях медицины применяют счетчики клеток. Счетчики определяют не только количество клеток в образце, но и их размеры и объем, что позволяет сделать предположение о виде клеточной структуры. Подобные приборы позволяют автоматизировать подсчет клеток, определение их размеров и объема, что исключает субъективный фактор и возможность получения ошибочных данных, а также упрощает процедуру и позволяет получить результаты в короткий срок. На основе использования методов индуктивного вывода предложена методика построения гипотез о взаимосвязи комбинации цитокинов с пролиферативной активностью клеток. Методика учитывает синергическое взаимодействие цитокинов и использует последовательное построение логических формул для отбора групп цитокинов, статистический анализ таблиц сопряженности и логическую интеграцию полученных оценок. Реализация предложенной методики в рамках ИС позволит существенно ускорить научные исследования в этой области. Приведена итоговая методика построения гипотез о взаимосвязи комбинации цитокинов с биологической активностью клеток The paper considers a comparison of experimental distributions of the number of cells to determine the cytological and immunological effect of the simultaneous action of ophthalmic drugs Broxinac® and Oftalmoferon® on cells from the conjunctiva of a sick person, aimed at improving the methodology for assessing combinations of ophthalmic drugs in vitro. Preclinical studies make it possible to determine the effectiveness of the use of drugs, possible contraindications and side effects, in order to further determine the volume of clinical trials and the very possibility of their conduct. Recently, cell counters have been used in various fields of medicine. Counters determine not only the number of cells in the sample, but also their size and volume, which allows us to make an assumption about the type of cell structure. Such devices allow automating the counting of cells, determining their size and volume, which eliminates the subjective factor and the possibility of obtaining erroneous data, and also simplifies the procedure and allows you to get results in a short time. Based on the use of inductive inference methods, a method is proposed for constructing hypotheses about the relationship between the combination of cytokines and the proliferative activity of cells. The method takes into account the synergistic interaction of cytokines and uses the sequential construction of logical formulas for the selection of groups of cytokines, statistical analysis of contingency tables and logical integration of the estimates obtained. The implementation of the proposed methodology within the Information System will significantly accelerate research in this area. The final technique for constructing hypotheses about the relationship of the combination of cytokines with the biological activity of cells is presented

Selection of Endpoints for Clinical Studies of Ophthalmic Drugs

Until now, there have been no effective treatments for some ophthalmic diseases that have high social significance. Development of therapeutic approaches to such diseases may be complicated due to challenges in diagnosis and selection of clinical trial endpoints. The aim of the study was to analyse current approaches to selection of endpoints in clinical trials of ophthalmic drugs. Clinical efficacy studies of new medicinal products use surrogate endpoints in addition to clinical endpoints. However, currently used surrogate endpoints are not always relevant and do not fully reflect changes in the status of patients with chronic or progressive diseases. The study analysed published approaches to the selection of endpoints in clinical studies of ophthalmic drugs intended for the treatment of glaucoma, uveitis, dry eye syndrome, and age-related macular degeneration. It was demonstrated that the choice of surrogate endpoints in a clinical trial should take into account specific aspects of a particular disease. The assessment of dynamic patterns of changes in visual functions generally requires a complex approach for a comprehensive characterisation of the eye condition in a particular disease. The paper analyses the possibility of using potential surrogate endpoints in studies of the most common eye diseases, and highlights that none of them has been recommended for use in clinical trials or routine clinical practice.

Pharmacoeconomical approaches for assessing the rational use of ophthalmic drugs in polyclinic settings

Purpose. To evaluate the results of the rational use of ophthalmic medicines with the use of pharmacoeconomical analysis. Material and methods. With the help of ABC-VEN analysis, a comparative study of the quality of pharmacotherapy and drug provision of patients who were monitored and treated by an ophthalmologist of the polyclinic in 2015 and 2019 was conducted. Results. As a result, it was found that the share of costs for vital drugs increased by 10.1% and amounted to 71.1% in 2019, which corresponds to the standardized criterion (70-80%). There was a reduction in the cost of purchasing secondary drugs by 7.6%, which indicates a rational drug supply of ophthalmic drugs. The most commonly used drugs for the treatment of glaucoma were 27.8% in 2015 and 35.1% in 2019. The share of their acquisition costs was 54.9% and 67.9%, respectively. There was a significant increase in the range and number of drugs for the treatment of patients with glaucoma: a 2.8-fold increase in the number of purchased eye drops for monotherapy and a 12% increase in the number of combined drugs. Conclusion. Pharmacoeconomical analysis showed an optimization of spending money on the purchase of drugs used in ophthalmology: an increase of 10.1% in the share of vital drugs and a decrease of 7.6% in the cost of purchasing secondary drugs. There was an increase in the range and quantity of drugs for the treatment of patients with glaucoma. Key words: ABC-VEN-analysis, drugs, ophthalmology, pharmacoeconomics.

Contact Lenses as Ophthalmic Drug Delivery Systems: A Review

Ophthalmic drugs used for the treatment of various ocular diseases are commonly administered by eye drops. However, due to anatomical and physiological factors, there is a low bioavailability of the active principle. In order to increase the drug residence time on the cornea to adequate levels, therapeutic contact lenses have recently been proposed. The polymeric support that constitutes the contact lens is loaded with the drug; in this way, there is a direct and effective pharmacological action on the target organ, promoting a prolonged release of the active principle. The incorporation of ophthalmic drugs into contact lenses can be performed by different techniques; nowadays, the soaking method is mainly employed. To improve the therapeutic performance of drug-loaded contact lenses, innovative methods have recently been proposed, including the impregnation with supercritical carbon dioxide. This updated review of therapeutic contact lenses production and application provides useful information on the most effective preparation methodologies, recent achievements and future perspectives.

Development of an In Vitro Blink Model for Ophthalmic Drug Delivery

Purpose: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using computer-aided design software and printed using a stereolithography 3D printer. The eyelid and eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min. Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation, nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL) than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05). Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better results than a simple, static vial incubation model.