Povezanost perifernih morfoloških promjena mrežnice i genotipskih promjena u bolesnika sa senilnom makularnom degeneracijom [The association of the peripheral morphological retinal changes and genotypic changes in the patients with age-related macular degeneration]

Abstract

Age-related macular degeneration (ARMD) is a multifactorial neurodegenerative disease of macular region of the retina and is a leading cause of visual loss of elderly people in developed countries. Early signs of the disease are characterized by the presence of the visible soft drusen, areas of hyperpigmentation or depigmented areas, whereas later stages manifest as either choroidal neovascularization (CNV) or atrophy of photoreceptors and retinal pigment epithelium. In the last decade the risk assessment was based on the clinical examination of the macular region, clinically the easiest one to approach to. Recent clinical data showed that the pathologic changes could be found at the retinal periphery. Likewise, clinical studies confirmed a strong association of the CFH, ARMS2, HtrA1, C2,CFB and C3 susceptibility genes with ARMD. The reports that linked the peripheral retinal changes and nucleotide polymorphisms of the susceptibility genes have analysed peripheral retina with standard fundus camera which can analyze only 30-50 degrees at once. The aim of this study is to determine the association of the peripheral retinal changes and genotypic changes in ARMD and their implications on the course and prognosis of the disease. The inclusion criteria were the age (older than 50) and the presence or absence of the clinical signs of the disease. Depending on those criteria, they were referred either to ARMD or control group. We included 160 participants in ARMD group and 150 participants in the control group. All the participants have undergone the clinical examination, the wide angle fundus photographing, OCT of the macular region and DNA genotyping from extracted peripheral blood. 126 The results showed that there was no statistical significant difference in demographic characteristics (age, sex or habits) between those two groups. The peripheral drusen, peripheral reticular pigment and paving stone degenerations are more prevalent in ARMD group. Likewise, we found statistically significant difference in odd ratio for the association of the nucleotide polymorphisms and ARMD disease: In ARMD group, homozygotes rs10490924 have 17,83 times, rs1061170 2,01 times, rs11200638 16,02 times, rs1410996 8,33 times and heterozygotes rs10490924 2,19 times higher risk for ARMD than in control group. In the control group, we found statistically significant difference in odd ratio for the association of the nucleotide polymorphisms and control group: In the control group, heterozygotes rs4151667 2,70 times, rs641153 5,26 times, rs9332739 2,70 times and rs547154 7,69 times less risk for ARMD than in a disease group. Multivariante analysis of the magnitude of the association of peripheral retinal changes and maculopathy showed that patients with peripheral drusen have almost three times, those with RPP two times and with paving stone degenerations 4,5 times more risk for ARMD macular changes compared to the control group. In ARMD group, there was a strong association of the peripheral drusen and reticular pigment with polymorphism CFHY402H: for peripheral drusen OR=4,5for CC genotype and for RPP OR=4,49 for CC and OR=3,51 for CT genotype. When we analyze peripheral retinal changes and genotypic changes in all participants together with or without signs of maculopathy, we found that peripheral drusen and RPP are statistically significant more present in the participants with polymorphisms of CFH, ARMS2 and HTRA1 genes. We also found that paving stone degenerations are statistically significant more present in the participants with polymorphisms ARMS2 and HtrA1 genes. There was no statistically significant association between hyperpigmentations, hypopigmentations, white without pressure, lattice degenerations, holes, retinoschisis and vitreal opacities with nucleotide polymorphisms in both groups. These results have shown the significance of the peripheral drusen and RPP and potentially paving stone degenerations in the fenotypic features of ARMD and therefore, defining their potential role in the classification of the disease, early detection and follow-up of the patients with ARMD