Ewa Matczyńska

The aim of the present study was to analyze the relationship of age-related macular degeneration (AMD) progression with clinical characteristics, demographic, and environmental risk factors that would affect disease development. In addition, the influence of three genetic AMD polymorphisms (CFH Y402H, ARMS2 A69S, and PRPH2 c.582-67T>A) on AMD progression was investigated. In total, 94 participants with previously diagnosed early or intermediate AMD in at least one eye were recalled for an updated re-evaluation after 3 years. The initial visual outcomes, medical history, retinal imaging data, and choroidal imaging data were collected to characterize the AMD disease status. Among the AMD patients, 48 demonstrated AMD progression, and 46 showed no disease worsening at 3 years. Disease progression was significantly associated with worse initial visual acuity (OR = 6.74, 95% CI = 1.24-36.79, p = 0.03) and the presence of the wet AMD subtype in fellow eyes (OR = 3.79, 95%CI = 0.94-15.2, p = 0.05). In addition, a higher risk of AMD progression appeared in the patients with active thyroxine supplementation (OR = 4.77, CI = 1.25–18.25, p = 0.002). The CC variant of CFH Y402H was associated with AMD advancement compared to the TC+TT phenotype (OR = 2.76, 95% CI: 0.98–7.79, p = 0.05). Identifying risk factors of AMD progression may lead to earlier intervention and better outcomes, preventing the expansion of the late stage of the disease.

Age-related macular degeneration (AMD) is a common retina degenerative disease with a complex genetic and environmental background. This study aimed to determine the polygenic risk score (PRS) stratification between the AMD case and control patients. The PRS model was established on the targeted sequencing data of a cohort of 471 patients diagnosed with AMD and 167 healthy controls without symptoms of retinal degeneration. The highest predictive value to the target dataset was achieved for a 22-variant model with a p-value lower than threshold P_T = 0.0123. The median PRS for cases was higher by 1.1 than for control samples (95% CI: (−1.19; −0.85)). The patients in the highest quantile had a significantly higher relative risk of developing AMD than those in the lowest reference quantile (OR = 35.13, 95% CI: (7.9; 156.1), p < 0.001). The diagnostic ability was investigated using ROC analysis with AUC = 0.76 (95% CI: (0.72; 0.80)). The polygenic susceptibility to AMD may be the starting point to expand AMD diagnostics based on rare highly penetrant variants and investigate associations with disease progression and treatment response in Polish patients in future studies.

Age-related macular degeneration (AMD) remains the leading cause of blindness in elderly people, but the pathophysiology of this disease is still largely unknown. We investigated the systemic expression of angiogenesis-regulating growth factors and selected miRNAs known to regulate angiogenesis in AMD patients. We also focused on possible correlations of their expression with the presence of CFH Y402H or ARMS A69S risk variants. A total of 354 AMD patients and 121 controls were enrolled in this study. The levels of angiogenesis-regulating factors were analyzed in plasma samples using Luminex technology. The expression of selected miRNAs was analyzed in peripheral blood plasma using real-time qPCR. The genetic analysis was performed with an Illumina NextSeq500 system. AMD was an independent factor associated with lower levels of angiogenin (β = −0.29, p < 0.001), endostatin (β = −0.18, p < 0.001), FGF-basic (β = −0.18, p < 0.001), PlGF (β = −0.24, p < 0.001), miRNA-21-3p (β = −0.13, p = 0.01) and miRNA-155-5p (β = −0.16, p = 0.002); and with higher levels of FGF-acidic (β = 0.11, p = 0.03), miRNA-23a-3p (β = 0.17, p < 0.001), miRNA-126-5p (β = 0.13, p = 0.009), miRNA-16-5p (β = 0.40, p < 0.001), miRNA-17-3p (β = 0.13, p = 0.01), miRNA-17-5p (β = 0.17, p < 0.001), miRNA-223-3p (β = 0.15, p = 0.004), and miRNA-93 (β = 0.11, p = 0.04). The expression of analyzed miRNA molecules significantly correlated with the levels of tested angiogenesis-regulating factors and clinical parameters in AMD patients, whereas such correlations were not observed in controls. We also found an association between the CFH Y402H polymorphism and miRNA profiles, whereby TT homozygotes showed evidently higher expression of miRNA-16-5p than CC homozygotes or TC heterozygotes (p = 0.0007). Our results suggest that the balance between systemic pro- and anti-angiogenic factors and miRNAs is vital in multifactorial AMD pathogenesis.