The dissertation is dedicated to solving of a challenging problem of the current ophthalmology – to improve the quality of surgical treatment of diabetic maculopathy (DMP) in patients with diabetic retinopathy (DR) and type 2 diabetes (T2D) on the ground of studying the new elements of its pathogenesis, determining risk factors and prognostication of development and progression, as well as relapses after the surgical treatment.
The scientific data about the DMP relapses after the vitreoretinal interventions were amplified. By their character and clinical course the relapses were divided into early transitional (occurred in the month 1-3 and disappeared later), early persistent (occurred in the month 1-3 and then remained for 6-12 months ) and late (occurred after 6-12 months and not regressed).
It was identified for the first time that in patients, who do not have DMP and who are on the early stages of DR, PL hyperreactivity to adrenalin and collagen was detected. The risk factors of DMP progression associated with NPDR included the increase of purine receptor reactivity, the stereotypical factors of DME included АТ1- and PAF-receptors hyperreactivity.
It was identified for the first time that the DMP and DME progression in patients with PDR caused hyperreactivity of PL purine receptors in the setting of АТ1- and PAF-receptors hyperreactivity. In the presence of dominant PL reactivity to collagen the development of DME was limited.
The scientific data about the pathogenic significance of repeated increase of ET1 level in the blood of the patients with DMP: the minimal hormone level was observed with the primary NPDR and the maximal level was observed with PDR, were made more specific. The high ET1 level defined the early persistent relapses of DMP after the surgical treatment.
High TNFα level defined DMP relapses after vitreoretinal interventions regardless of their type. The highest effect of TNFα was observed on the occurrence of the early persistent relapses.
It was identified for the first time that in the Ukrainian patient cohort the gene TNFα rs1800629 polymorphism was associated with DMP development. The genotypes with the minor A allele increased the risk of DMP development. High TNFα level in the blood of the carriers of allele A of gene PDGFB rs1800818 polymorphism was a pathogenetic factor of DMP relapses and it was associated with the higher central retinal thickness (CRT) before the surgical intervention as well as during 1 year of follow up compared to the allele G carriers.
The scientific data regarding the role of the PDGF-BB level in the blood of the patients with DMP in the setting of moderate to severe NPDR and PDR (p<0.001) were made more specific. It was identified for the first time that the high blood level of PDGF-BB before the surgical treatment defined the relapses of DMP: the regressional model of relapses development depending on the initial level of PDGF-BB had the prognostic accuracy of 89,8% (p<0,001), which proved its pathogenetic significance.
New information was added to the scientific data about the association of gene PDGFB rs1800818 polymorphism with DMP in the Ukrainian patients: a minor allele С diminished the risk of DMP. It was identified for the first time that gene PDGFB rs1800818 polymorphism was associated with DMP relapses after the surgical treatment: the relapse risk in the minor allele С carriers was substantially diminished (OR=0,07; PI 0,04-0,12; р<0,001).
It was identified for the first time that the allele C carriers had lesser PDGF-BB level compared to the allele T carriers, what explained the protective effect of gene PDGFB rs1800818 polymorphism regarding the development of DMP relapses.
Pathogenic factors of DME risk were demonstratively identified for the first time with the help of the mathematical modeling and these risks appeared to be the increase of PL aggregation due to angiotensin-2 (An-2), PAF and collagen influence. The etiological factors of DMP relapses were polymorphisms of gene PDGFB rs1800818 and gene TNFα rs1800629, and the pathogenetic factors were increases of the blood levels of PDGF-BB and TNFα. The significant factors of DME relapses after the surgical interventions were the genotypes of polymorphisms of gene PDGFB rs1800818 and gene TNFα rs1800629, blood level of PDGF-BB and CRT before the surgical intervention.
A project of the working classification of the DMP relapses after surgical treatment in patients with DR and T2D was developed. It included the types of relapses, the terms of the relapses occurrence after the surgical treatment, clinical source, and treatment methods.
Mathematical models of prognostication of DMP after surgical treatment were developed, as well as a calculator of prognosis in the Excel operating environment.
