It is estimated that there are approximately 10,000 patients with RP in Poland. Taking into account the inclusion criteria, recruitment duration, the specificity and innovative nature of the experiment, and logistical constraints, the investigators planned to recruit 60 adult patients with RP who met both the inclusion and exclusion criteria. The diagnosis of RP will be made based on the characteristic clinical picture: (i) a typical RP fundus appearance with a waxy pallor of the optic disc; (ii) reduced retinal vessel diameter and intraretinal pigment deposits in the central periphery of the fundus; (iii) a history of progressive night and/or color vision impairment, peripheral vision loss, photophobia, reduced visual acuity, and prolonged dark adaptation; (iv) peripheral narrowing, even to "tunnel vision" on visual field testing. Additionally, to confirm the diagnosis, Next-Generation Sequencing (NGS) will be performed, covering all known genes responsible for retinal dystrophic diseases, or genome analysis using whole exome sequencing (WES). Furthermore, each patient will undergo full-field electroretinography (ERG), where the expected result for RP indicates a significant reduction or inability to detect a response from the peripheral retina. It is worth emphasizing that appropriate selection criteria, combined with the pioneering combination of a detailed functional and morphological assessment of the eyeball subjected to SML and cytogenetic analysis, could represent a breakthrough in the search for the first effective standard of treatment for RP.
It is noteworthy that the diagnosis is usually made in the 2nd or 3rd decade of life, the gradual progression of visual impairment with predicted vision loss, and the lack of effective treatment options make the diagnosis of RP emotionally devastating. This disease is progressive, leading to progressive blindness and permanent disability within a few years of diagnosis. This poses a significant problem for patients, their caregivers, the healthcare system, and society as a whole. Furthermore, the inability to independently perform previously achievable activities and dependence on others lead to frustration and low self-confidence, leading to life dissatisfaction and depressive symptoms. Consequently, patients with RP experience decreased motivation to perform daily tasks, including work, which ultimately burdens the social and welfare system. On the other hand, the progressive nature of RP forces patients to constantly adapt to daily challenges, which become increasingly difficult due to deteriorating visual function. The deteriorating quality of life scores in patients with RP, depending on disease progression, indicate that visual replacement skills may not be sufficient to cope with social interactions in the advanced stages of the disease. This condition is currently incurable due to the lack of causal therapy. Moreover, due to the multifactorial nature of the condition, including a combination of environmental and genetic factors, developing causal treatments for RP is an extremely difficult challenge. Furthermore, there is currently no effective symptomatic therapy to inhibit disease progression. Therefore, there is an urgent need to find effective treatment methods and correlate treatment response with phenotypic and genotypic conditions, also in the Polish population. The use of the increasingly widely available, inexpensive method of non-invasive retinal stimulation using SML to induce immunomodulatory and regenerative effects on damaged photoreceptors raises hopes for the first effective treatment to inhibit disease progression in RP.
There are only few reports in the medical literature on the relationship between the severity of retinal degeneration in the RP and disturbed expression of microglia and proinflammatory cytokines. However, no detailed analysis of this issue, especially in the context of the genetic profile, as well as its potential use in the development of therapeutic methods of the RP has been carried out. The introduction of SML to the treatment of retinal diseases has revolutionized the way laser therapy is perceived in ophthalmology. During SML, laser energy is delivered to the retinal pigment epithelium (RPE) in the form of a series of very short pulses, between which there are pauses to allow the tissue to cool down, so no damage to the cells is caused. It has been shown that this energy activates the heat shock proteins in RPE. The mode of action of these proteins is based on their anti-inflammatory and anti-angiogenic effects and cause the local increase in cytokine concentration which leads to the induction of acute inflammation. The consequence of this condition, caused by the induction of an immunomodulatory effect, is the reduction of the chronic inflammation responsible for the formation of degenerative changes in the retina. Moreover, the process of protein secretion by the RPE optimizes and improves functioning of the retina. This mechanism may be important especially in degenerative diseases of the retina, where there is a progressive impairment of the RPE function. It is worth emphasizing that this method is not associated with the risk of permanent damage to the retina and no side effects have been described so far. In the world literature, only two analyzes of the effectiveness of the red SML stimulus in the eyes from RP have been reported so far, showing significant benefits in terms of improving visual acuity, visual field and function of the retinal ganglion cells. It should be noted, however, that this material concerned a retrospective evaluation with a short observation period of 1 month and was carried out on a limited number of patients. Additionally, the selection of diagnostic methods did not provide a complete assessment of the dynamics of functional changes in the retina. Moreover, it seems that such a short time of observation of patients does not allow to differentiate the short-term effect of the applied therapy and the physiological fluctuations in the parameters of the organ of vision in the course of RP. Importantly, no study using the innovative yellow SML stimulus in the panmacular protocol in the eyes of the polish inhabitants has been published so far. In conclusion, the available material is too limited to define the effect of the SML stimulus on immunomodulatory processes and define SML as a recommended treatment procedure for RP.
The planned medical experiment is the first comparison of the neurostimulatory effects of two SMLs on the RP, of which one (red) has already shown some efficacy in this disease entity, but there is no agreement between researchers as to the optimal retinal laser protocol. The second laser (yellow) is, in turn, a representative of the new generation of these devices with a shorter wavelength, which may increase the safety of the procedure with the simultaneous intensification of action in the area of the damaged retina. Additionally, the innovative nature of the project is supported by the fact that it will be the first experiment to determine the cytogenetic profile in patients with RP in combination with the evaluation of the modulation of proinflammatory, neurotrophic and angiogenic factors in tears and peripheral blood as well as functional changes of the eyeball in the course of using both SML.
The meticulous study protocol was provided in corresponding sections of the clinical trial registration form.
