The aim of Activity I of the Lublin Digital Union project is to create a system for monitoring the progression of retinitis pigmentosa (RP) depending on the mutation causing the disease, using neural networks in 200 patients with different types of RP inheritance in the Polish population. We invite you to read an interview with Prof. Katarzyna Nowomiejska, MD, from the Department and Clinic of General and Paediatric Ophthalmology at the Medical University of Lublin/ USK1, who, as the content manager, supervises the implementation of Activity I in the LUC Project
RP is the most common rare genetic eye disease and constitutes a broad group of retinal dystrophies. RP is caused by mutations in various genes encoding proteins involved in the visual process in the retina. Our research within the project will ultimately cover 200 patients with various mutations of genes involved in the process of vision. RP is a very diverse, i.e. heterogeneous, disease. It involves different types of inheritance, different mutations in different genes, and different courses of the disease. All these make it very difficult to determine patterns in the course of the disease. In some patients, RP progresses very quickly – they lose their vision, even going blind at a young age, while in others, their vision deteriorates very slowly throughout their lives. In this disease, clusters of pigment form in a specific shape at the back of the eye. It looks similar in both eyes, but the pattern is different in each patient.
Research conducted as part of the LUC project.
In Activity I, we perform retinal examinations on all patients, including visual function tests, visual acuity and visual field tests, as well as retinal structure and thickness tests, observing whether there is any progression of changes after one year and after two years. Genetic testing is performed at the University of Life Sciences to determine which mutation causes the disease. This is unique in Poland, as this type of testing is not reimbursed by the National Health Fund. Patients would not be able to benefit from such testing free of charge.
Therefore, the most important thing for us is to perform genetic testing using sequencing to determine which genes have pathogenic variants in their DNA sequence. We then group these patients according to the mode of inheritance. We have noticed that among 200 RP patients, there are many types of genes with abnormalities.
Conducting the study. The role of partners.
LUC’s tasks are divided among the project partner teams. In our clinic, blood is collected from patients and, based on blood samples, genetic testing is performed at the University of Life Sciences. Lublin University of Technology uses AI tools to evaluate the imaging tests we perform in our clinic. We are currently after the first round of testing; patients have undergone one test. The team of IT engineers has already been able to assign images of the fundus to specific mutations.
It should be emphasised that, to date, there have been no studies on such a scale in the Polish population that would allow us to determine which genes are most likely to carry mutations causing RP. This is a significant added value to the Lublin Digital Union project!
It should be remembered that each population and each nationality has its own genetic differences, although we know that migration occurs and this affects the mixing of genes. There are populations in which certain genes have more mutations. Based on the patient’s clinical picture, i.e. their phenotype, we select a panel, or a set of genes, which are tested to obtain the genotype, i.e. abnormalities in the genes.
What we know about patients with retinitis pigmentosa.
Most RP patients are generally healthy, suffering only from visual impairment, but these impairments progress throughout their lives. In approximately 80% of cases, RP is a non-syndromic disease – the patient only experiences visual impairment. Only in about 10-20% of patients is it a syndromic disease, i.e. with symptoms affecting other organs. Therefore, in the study group, we have individuals with Usher syndrome, who additionally have hearing problems, and individuals with Bardet-Biedl syndrome, who, in addition to RP, suffer from obesity, infertility and kidney dysfunction, but such patients are in the minority.
Rare diseases in ophthalmology
Retinal pigment degeneration is currently an incurable disease, although clinical trials of various gene therapies, which are very expensive, are ongoing worldwide. In Poland, there is currently no form of therapy available, as is the case with 90% of all rare diseases for which there is no treatment. People with rare diseases face many problems in their everyday lives. First and foremost, they have no prospect of improvement in their health and live with the knowledge that the disease will progress over the course of their lives. Patients with rare diseases often suffer from depression as a result. Genetic diagnostics, whose development we are witnessing at the moment, are not readily available. Many patients’ stories describe a very difficult journey from the first symptoms to the diagnosis of the disease: visits to various specialists, undergoing diagnostics at different centres and long waits for a diagnosis.
Ophthalmology is a field that has seen a lot of developments in recent years, in terms of new technologies, surgical techniques and pharmacology. Patients can benefit from new therapies for “common” diseases such as cataracts and age-related macular degeneration, while rare diseases have so far been pushed to the margins of mainstream clinical practice. There have been and still are relatively few patients with rare eye diseases, so efforts to develop new drugs are not cost-effective, especially since the patient group is heterogeneous. We have taken on a topic where we objectively need detailed knowledge about the disease. The 200 patients to be studied in the project constitute an objectively large research group for a rare disease. This gives us considerable opportunities to gain in-depth knowledge about the specifics of this disease and will allow us to use the potential of artificial intelligence for better diagnosis and, in the future, treatment.