To assess the capacity of the structural and functional tests used in ophthalmology to study the neurodevelopmental axonal and neurological deterioration that occurs at a systemic level in demyelinating diseases such as multiple sclerosis or Dèvic’s neuromyelitis and in other neurodegenerative diseases such as Alzheimer’s, mild cognitive impairment, or Parkinson’s.
Complete a follow-up study in subjects with these pathologies with annual check-ups, to correlate the observed changes with those recorded in their functional status and neuroimaging tests. Undertake a study of the quality of life and severity of the pathology in these subjects and analyze if it relates to the state of the nerve fiber layer of the retina. Finally, to analyze if the changes observed in the nerve fiber layer of the retina during the follow up are able to predict which treatments are the most effective in controlling the axonal damage associated with these diseases.
María Satué, Elisa Vilades, Elvira Orduna, Maria Jesús Rodrigo, Sofía Otín, Luis Pablo Júlvez, Javier Obis, Héctor Gracia, José Manuel Larrosa, Laura Gil Arribas, Vicente Polo, Javier Ascaso, José Ramón Ara, Jesús Martín, Isabel Dolz, Carmen Almarcegui, Javier Fernández, Mª Isabel Fuertes.
The main objective is to develop clinical tools aimed at the assessment of visual function and visual cognitive abilities in children from the preverbal ages. This will allow us to describe the development of each of the visual functions from birth to adulthood, as well as to assess the influence of certain perinatal factors in this process.
METHODOLOGY As a first step in this project, we have designed, standardized and validated the PreViAs (Preverbal Visual Assessment) ® questionnaire. We are currently assessing its diagnostic capacity in the short and medium term. Secondly, we are completing the development of a digital platform with visual tests tailored to children of any age. This project includes validation of each test and normalization for all ages.
Inmaculada González, Esther Prieto, Irene Altemir, Teresa Pérez, Olimpia Castillo, Álvaro Fanlo y Javier Gutiérrez.
To evaluate the usefulness of different methods of diagnostic imaging for the diagnosis and follow-up of glaucoma, as well as that of a set of tests to evaluate visual function and quality of life. The main purpose will be to try to identify those diagnostic methods that are able to detect the existence of disease and the progression of glaucomatous damage at an early stage. In addition, there is the question of knowing the situation in terms of visual function (not only “how much” but “how” they see) and what is the quality of life of patients with glaucoma in our health area, in order to improve the clinical-care approach.
The study group will consist of patients diagnosed with simple chronic glaucoma and of ocular hypertensive patients (with or without treatment) originating from our clinics who meet the criteria for inclusion in the study. A complete ophthalmic examination will be carried out, including a set of structural evaluation tests of the optic nerve and retinal nerve fiber layer, as well as visual function tests and quality of life assessment.
Noemí Güerri, Blanca Ferrández, María Pilar Bambó, Beatriz Cameo, Ruben Hernández Vián, Susana Pérez-Oliván, José M. Larrosa, Luis Pablo Júlvez, Mª Isabel Fuertes.
To compare plasma levels of inflammatory mediators in patients with diabetic macular edema and different degrees of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus compared to healthy controls. To evaluate OCT and SD-OCT Swept-source OCTs in type 2 diabetic patients versus healthy controls. To relate anthropometric parameters according to the degree of DR. To evaluate the relationship between parameters of central macular thickness obtained by OCT and glycosylated hemoglobin values. And finally to assess macular ischemia by OCT angiography in type 2 diabetic patients versus healthy controls.
Prospective, longitudinal study with more than 100 patients included. All patients underwent a complete ophthalmic examination protocol including visual acuity, IOP, fundoscopy, and SD-OCT and SS-OCT ratios.
Antonio Ferreras, Beatriz Abadia, Guayente Verdes, Fran Bartol, Carlos Isanta, Oscar Ruiz-Moreno, Emilio Abecia, Jorge Sierra, Mª Isabel Fuertes.
PROJECT “DESCEMET MEMBRANE ENDOTHELIAL KERATOPLASTY (DMEK)”, with the objective of evaluating the physical and anatomical changes at the corneal level and in visual quality that occur after Descemet’s endothelial membrane keratoplasty. In this project the evaluation and monitoring of patients undergoing the DMEK technique are performed by devices that analyze the corneal structure and its functionality. To compare the evolutionary changes in the time in these patients in the postoperative period of the surgery, and to analyze the differences existing after the stabilization of the cornea between these patients and healthy subjects.
PROJECT “PTERYGIUM SURGERY”, with the aim of evaluating the efficacy of the fibrin membrane “Endoret®(prgf®)” used as a graft in Pterygium surgery compared to the conjunctival autograft technique. The methods are to analyze the anatomical (macroscopic and ultrastructural) and functional results of the “Endoret®(prgf®)” graft after Pterygium surgery and to compare them with the use of conjunctival autograft.
PROJECT “VISUAL QUALITY IN KERATOCONUS”, with the objective of evaluating the changes produced in the visual quality of patients undergoing keratoconus treatment. This project analyzes the results obtained with different visual quality tests (contrast sensitivity, aberrometry, OQAS, etc) after different surgical procedures performed in keratoconus surgery (Cross-linking, intracorneal segments, keratoplasty).
PROJECT “CLINICAL TESTS ON THE EFFICACY OF RGTA AFTER CORNEAL CROSSLINKING IN PATIENTS WITH KERATOCONO” with the objective of evaluating the efficacy of a corneal matrix regenerative agent (RGTA) in corneal reepithelization after cross-linking in patients with keratoconus. For this project the evolution and resolution of epithelial defects, as well as the monitoring of pain, that are experienced after the corneal cross-linking procedure and evaluated compared with controls (those without application of the product).
PROJECT “MEIBOMIAN GLAND DYSFUNCTION”, with the objective of evaluating the efficacy of different therapies for meibomian gland dysfunction (MGD). The methodology is to evaluate the clinical and visual quality changes after treatment with different treatments for MGD (different thermal methods, intense pulsed light, etc).
PROJECT “NEW TREATMENTS FOR DRY EYE SYNDROME”,, which evaluates the efficacy of different treatments for the control of inflammation, tear stability and blocking of different sensitivity receptors involved in dry eye syndrome or keratoconjunctivitis sicca (KCS). They are randomized, double-blind clinical trials.
PROJECT “CORNEAL EDEMA”, which evaluates the efficacy of a new ophthalmic solution for the reduction of corneal edema. It is a randomized, double-blind clinical trial.
PROJECT “CONJUNTIVITIS”, another randomized, double-blind clinical trial, aims to evaluate the efficacy of a new ophthalmic solution in the treatment of infectious conjunctivitis.
PROJECT “CONJUNTIVOCHALASIS”, has been undertaken for the validation and standardization of the surgical technique for the correction of symptomatic conjunctivochalasis (CCh).
PROJECT “VISUAL QUALITY OF LIOS PREMIUM IN PATIENTS WITH DRY EYE”,which tries to identify patients with poor visual quality after lens surgery with ocular or multifocal lenses that are due to alterations in the ocular surface. For this purpose, we will evaluate the symptoms, clinical parameters and visual function obtained after the surgery of crystalline lens with “premium” lenses in which an excellent visual quality has not been obtained.
PROJECT “VISUAL QUALITY AFTER SURGERY USING PREMIUM IOLs IN PATIENTS WITH DRY EYE SYNDROME”, aims to identify patients with poor visual quality after lens surgery with ocular or multifocal lenses due to alterations in the ocular surface. For this purpose, we will evaluate the symptoms, clinical parameters and visual function obtained after crystalline lens surgery using “premium” lenses in which an excellent visual quality has not been obtained.
PROJECT “CHARACTERIZATION OF SUBTYPES OF DRY EYE SYNDROME”, evaluates different diagnostic methods performed in patients with dry eye syndrome to characterize the different subgroups in which a multidisciplinary and etiological treatment can be performed. Patients with dry eye syndrome are diagnosed by means of a complete ordered sequence of diagnostic tests (tear osmolarity, questionnaires, clinical and automated tests of tear stability, tear secretion and volume, cell damage, tinctures, meibography, visual quality, etc) with which they are comprehensively characterized according to the different subgroups of DES. Clinical changes, visual function and quality of life are evaluated after personalized therapeutic interventions with adjustment according to the etiological origin of the disease.
Carry out follow-up studies in subjects with these pathologies with annual check-ups, in order to correlate the observed changes with those recorded in their functional status and neuroimaging tests. To analyze the quality of life and severity of the pathology in these patients and analyze whether it relates to the state of the nerve fiber layer of the retina. Finally, to analyze if the changes observed in the nerve fiber layer of the retina during the follow up are able to predict which treatments are the most effective in controlling the axonal damage associated with these diseases.
Miriam Idoipe, María Satué, Eduardo del Prado, Gloria López, Alejandro Blasco, Diana Soriano, Antonio Sánchez, Carlos Brito, Alicia Gavín, María Romero.
To evaluate the results obtained in a high performance service dedicated to cataract surgery (ARCCA), comparing different instruments and formulas used for the calculations of the intraocular lens used in this surgery. Check the results obtained with new premium intraocular lenses, both bifocal and trifocal as well as toric.
Study the refractive results obtained in the patients operated on in the ARCCA initiative and evaluate them according to the formulas used for the calculation of the intraocular lens. Search for a custom formula calculation choice according to myopic, hyperopic patients, and according to the characteristics of their anterior segment. Compare the results of standard intraocular lenses used in daily clinical practice with the new “Premium” lenses, which seek to obtain a personalized visual result, with maximum independence of glasses after surgery.
Galadriel Gimenez, Irene Altemir, Francisco Bartol, Paula Talavero, Francisco Javier Castro, Vicente Polo y Luis E. Pablo.
To evaluate the safety and efficiency of new formulations of retard liberation for treatment of experimental chronic glaucoma in animals.
We are developing and characterizing new biodegradable formulations of biomedical application for the creation of a new experimental model of chronic glaucoma in animals, and also for the treatment of this pathology. We are evaluating the hipotensor and neuroprotector effects of the formulations in the eye, by the controlled and supported liberation of the active drugs their intravitreal injection. We are inducing degeneracy of the optical nerve in rats by ocular hypertension by means of sclerosis of the epiescleral veins with hypersaline solution, to test the efficacy and safety of the new formulations. This research is needed, before to use new formulation in humans.
María Jesús Rodrigo, Rocio Herrero, Jesús Ruberte, David Ramos, Silvia Méndez, Teresa Ramírez, María José Cardiel, Milagros Chico, Manuel Subías, Teresa Martínez, Juan Luis Fuentes, Miriam Idoipe, Elena Garcia-Martin, Vicente Polo, Vanesa Andrés-Guerrero, Julián García-Feijoo, Pilar Pastoriza, Irene Bravo, María Loreto Salazar, Eugenio Vispe, Jose Antonio Mayoral, José María Fraile, José Manuel Larrosa, Carmen Luisa del Campo, y Luis E. Pablo.
Optometry is the science that studies the visual system in order to achieve maximum performance.
Irene Altemir Gómez, Galadriel Giménez Calvo, Alejandro Blasco Martínez, Diana Soriano Pina, Beatriz Cameo Gracia, Rubén Hernández Vián, Elvira Orduna Hospital, Sofía Otín Mallada, Elisa Viladés Palomar, Patricia Loma Lozano, Francisco Javier Segura Calvo, Álvaro Fanlo Zarazaga.
Clinical Trials Manager: Laura Gil
All research conducted on humans to determine or confirm clinical effects, and/or other pharmacodynamic effects, and/or to detect adverse reactions, and/or study the absorption, distribution, metabolism and excretion of one or more drugs under investigation in order to determine their safety and efficacy.
The Helsinki Declaration is the most important document in the ethics of research involving human subjects. Adopted by the 18th World Medical Assembly in Helsinki (Finland) in June 1964, it states that the doctor must protect the life, health, dignity, integrity, right to self-determination, privacy and confidentiality of the personal information of patients involved in research.
Participation of individuals in clinical trials should always be subject to their ability to consent in a free and voluntary way.
Informed consent involves a document that the patient signs voluntarily, accepting inclusion in the clinical trial by means of a positive act of decision involving altruism within society.
The Ethics Research Committee (ERC) is an independent, multidisciplinary body composed of healthcare professionals and lay members, whose purpose is to ensure the protection of the rights, safety and well-being of subjects participating in any biomedical research project.
The ERC must evaluate methodological, ethical and legal aspects of the projects prior to issuing an favorable judgement allowing the commencement of a clinical trial.
When the project reaches the researcher, having been sanctioned by the legal and ethical filter of the ERC, the researcher becomes the ultimate ethical filter, and with his knowledge of good clinical practices, and in compliance with the principles of “respect for persons, beneficence and justice” (Belmont Report, 1979), the clinical trial can be undertaken according to professional experience. All researchers in any one trial must be trained in good clinical practices and they should know and apply research ethics. Likewise, they have to complete numerous training sessions prior to the execution of each clinical trial.
The Sponsor: The sponsor of a clinical trial is the individual, company, institution or organization who has possession of the initial idea of the particular clinical trial. The sponsor is responsible for the initiation, management and/or financing of the clinical trial.
Trial monitors or CRAs (Clinical Research Associates): professionals in the field of health who develop activities related to medical research, mainly in the management and monitoring of clinical trials. Their work is based on their knowledge of all the aspects of a clinical trial, and in ensuring that each of the centers participating in the trial are familiar with the relevant protocols, they carry out their work in accordance with the requirements of the test protocol, good clinical practice and applicable legislation.
Protocol: The protocol is the document that contains all the information on the design, methodology and organization for conducting the clinical trial.
The development of new drugs follows a series of stages (phases I-IV), which begin once the molecule has been synthesized, biological tests have been performed and animal studies have been completed.
The aim here is to define the optimal dose, to demonstrate its safety and tolerability, to define the toxicity profile and to establish the pharmacokinetic characteristics of the research product.
The objective of this phase is to determine the efficacy of the product, establish the dose-response relationship and to further enhance the safety data obtained in phase I.
In this phase the intention is to evaluate the safety and efficacy of the treatment in conditions similar to those in future administration of the product under investigation in the general population, so the sample of subjects is broader. The drug will be compared with standard preestablished treatments, if any, or with a placebo if there are none.
Consists of monitoring the drug once it has been licensed and marketed, in search of long-term efficacy and safety.
“Whatsoever I shall see or hear in the course of my profession, as well as outside my profession in my intercourse with men, if it be what should not be published abroad, I will never divulge, holding such things to be holy secrets.” (Hippocratic Oath 500 BC). In medical research the measures aimed at protecting the privacy of subjects participating in a clinical trial, is known as confidentiality. Researchers responsible for studies have a duty of confidentiality, that is to say they must not divulge personal information about a subject to anyone outside of the trial without specific permission from the subject. There are several methods that the researcher can employ to maintain confidentiality, for example using special codes to identify participants and maintaining a limited number of staff with access to such information. Likewise, it is the responsibility of the Ethics Committee to monitor that, in each study there are conditions that ensure confidentiality of information of trial participants. In this regard, the Committee assesses, prior to the commencement of the project, that the researcher uses informed consent, specifies what information will be collected, who will have access to it, and what measures will be taken to protect such information throughout the trial and henceforth after the trial has been completed. During the development of the project, the ethics committee ensures that the established conditions are fulfilled so that information is kept secure.
In the Ophthalmology service of Miguel Servet University Hospital we have undertaken clinical trials for more than 20 years. The areas in which these have been performed are in Glaucoma, Retina and Ocular Surface. The clinical trials team consists of a structured group of highly qualified professionals specifically chosen for the development of a particular trial. The constituent figures of each project are:
Has utmost responsibility for the correct execution of the trial.
Professionals in charge of performing consultations with patients according to protocol and fulfilling the ethical precepts.
Technician in charge of additional tests and data management.
The execution of clinical trials is subject to continuous audit and/or periodic inspections in the centers where the trials are undertaken. An audit consists of an independent, comprehensive and systematic review of activities and documentation, in order to assess whether such activities were implemented in accordance with the protocol, standard work procedures, standards of good clinical practice and valid legislation. Similarly, an inspection is an official review undertaken by a competent responsible authority (e.g. FDA- The regulatory body for the administration of medicines and foods in the United States) of all related elements within the trial. These authorities are bodies responsible for the protection of public health by means of the regulation of medicinal products for human and veterinary use, vaccines and other biological products, medical devices, food standards, cosmetics, dietary supplements and radiation-emitting products. In our long history of conducting clinical trials, we have successfully undergone numerous audits and inspections.