Furundaoturan Onur, Degirmenci Cumali, Afrashi Filiz, Atik Tahir, Akkin Cezmi, Mentes Jale, Nalcaci Serhad
Department of Ophthalmology, Ege University, Izmir, Turkey.
Department of Medical Genetics, Ege University, Izmir, Turkey.
Graefes Arch Clin Exp Ophthalmol. 2025 Apr;263(4):1167-1173. doi: 10.1007/s00417-024-06699-0. Epub 2024 Nov 27.
To evaluate the relationship between the presence of reticular pseudodrusen (RPD) and the risk allele of ARMS2 rs10490924 variation in dry-AMD patients by using multimodal imaging. Also, to compare patients with and without RPD and healthy volunteers according to the distribution of the risk allele.
In this cross-sectional study, dry-AMD patients with (Group A, n = 50) and without (Group B, n = 50) RPD and healthy volunteers (Group C, n = 50) were enrolled. After detailed ophthalmologic examination, confocal scanning laser ophthalmoscope (Heidelberg, Germany) was used to acquire near infra-red (NIR) imaging for RPD and the diagnosis was confirmed by Spectral Domain-Optical coherence tomography (Heidelberg, Germany). In silent choroidal neovascularization suspicion, optical coherence tomography angiography (Optovue, Fremont, CA) was performed and those were excluded. For genetic assessment, peripheric blood sampling was performed. Using next-generation sequencing technique (NGS), ARMS2 rs10490924 single nucleotide polymorphism was investigated. Groups were compared according to the distribution of the risky allele.
150 eyes of 150 participants were included. In Group A, 42% (21) of patients were heterozygous for the T risk allele, 30% (15) were homozygous, and the risk allele was not detected in 28% (14). In Group B, 44% (22) of patients were heterozygous, 17% (8) were homozygous, and the risk allele was not detected in 39% (20). In Group C, 30% (15) of participants were heterozygous, 4% (2) were homozygous, and variation was not observed in 64% (32). Homozygous participants in Group A were significantly higher than other two groups (Group A-B: OR = 2.67, 95% CI: 0.895, 8.020; Group A-C: OR = 17.14, 95% CI: 3.449, 85.208) while in Group B, homozygous individuals were higher than Group C (respectively, p values 0.0039, 0.0002, 0.013). T risky allele frequencies were 51%, 38%, and 20% in Groups A, B, and C, respectively, which was significantly higher in Group A (p = 0.02).
Genetic influence in AMD is inevitable while certain differences according to different ethnicities may apply. Association of genetic variations and imaging findings like RPD is lacking among literature for different populations. By the aspect of this study, the relationship between RPD and ARMS2 rs10490924 polymorphism in dry-AMD patients were highlighted among Turkish population by using multimodal imaging for the first time.
What is Known? Pathophysiology of age-related macular degeneration is influenced from multiple factors including single nucleotide polymorphisms. The variations of ARMS2 are suspected well in the current literature. Reticular pseudodrusen is related to advanced stages of age related macular degeneration disease. What is New? The ARMS2 rs10490924 risk genotype is associated with the presence of reticular pseudodrusen in dry age related macular degeneration patients. Homozygous genotype of T risk allele is evaluated significantly higher in dry age related macular degeneration patients with reticular pseudodrusen.
通过多模态成像评估干性年龄相关性黄斑变性（dry-AMD）患者中网状假性玻璃膜疣（RPD）的存在与ARMS2 rs10490924变异风险等位基因之间的关系。此外，根据风险等位基因的分布比较有和没有RPD的患者以及健康志愿者。
在这项横断面研究中，纳入了有RPD的干性AMD患者（A组，n = 50）、无RPD的干性AMD患者（B组，n = 50）和健康志愿者（C组，n = 50）。经过详细的眼科检查后，使用共焦扫描激光眼底镜（德国海德堡）获取RPD的近红外（NIR）图像，并通过光谱域光学相干断层扫描（德国海德堡）进行确诊。对于可疑的静止性脉络膜新生血管，进行光学相干断层扫描血管造影（美国加利福尼亚州弗里蒙特市Optovue公司）检查，并将这些患者排除。进行基因评估时，采集外周血样本。使用下一代测序技术（NGS）研究ARMS2 rs10490924单核苷酸多态性。根据风险等位基因的分布对各组进行比较。
纳入了150名参与者的150只眼睛。在A组中，42%（21例）患者为T风险等位基因杂合子，30%（15例）为纯合子，28%（14例）未检测到风险等位基因。在B组中，44%（22例）患者为杂合子，17%（8例）为纯合子，39%（20例）未检测到风险等位基因。在C组中，30%（15例）参与者为杂合子，4%（2例）为纯合子，64%（32例）未观察到变异。A组中的纯合子参与者显著高于其他两组（A组与B组比较：OR = 2.67，95%CI：0.895，8.020；A组与C组比较：OR = 17.14，95%CI：3.449，85.208），而在B组中，纯合子个体高于C组（p值分别为0.0039、0.0002、0.013）。A、B、C组中T风险等位基因频率分别为51%、38%和20%，A组显著更高（p = 0.02）。
年龄相关性黄斑变性中的遗传影响是不可避免的，同时可能因不同种族存在某些差异。不同人群的文献中缺乏遗传变异与RPD等影像学表现之间的关联。从本研究的角度来看，首次通过多模态成像在土耳其人群中突出了干性AMD患者中RPD与ARMS2 rs10490924多态性之间的关系。
已知内容是什么？年龄相关性黄斑变性的病理生理学受多种因素影响，包括单核苷酸多态性。目前文献中对ARMS2的变异有充分怀疑。网状假性玻璃膜疣与年龄相关性黄斑变性疾病的晚期阶段相关。新内容是什么？ARMS2 rs10490924风险基因型与干性年龄相关性黄斑变性患者中网状假性玻璃膜疣的存在相关。在有网状假性玻璃膜疣的干性年龄相关性黄斑变性患者中，T风险等位基因的纯合基因型评估显著更高。
