Grassmann Felix, Fleckenstein Monika, Chew Emily Y, Strunz Tobias, Schmitz-Valckenberg Steffen, Göbel Arno P, Klein Michael L, Ratnapriya Rinki, Swaroop Anand, Holz Frank G, Weber Bernhard H F
Institute of Human Genetics, University of Regensburg, Regensburg, D-93053, Germany.
Department of Ophthalmology, University of Bonn, Bonn, D-53127, Germany.
PLoS One. 2015 May 11;10(5):e0126636. doi: 10.1371/journal.pone.0126636. eCollection 2015.
Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2_rs10490924 [P < 0.00088] and C3_rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.
在全球范围内,年龄相关性黄斑变性(AMD)对50岁以上人群的视力丧失构成严重威胁,合并患病率约为9%。预计到2020年,受此病影响的人数将达到2亿。虽然表现为地图样萎缩(GA)的AMD病变存在高度个体差异,但对预后因素的了解甚少。在此,我们旨在阐明临床、人口统计学和遗传因素对GA进展的影响。通过分析目前关于GA病变生长的最大数据集(N = 388),我们的研究结果表明,三个因素对GA病变生长有显著且独立的影响,其中包括至少两个遗传因素(ARMS2_rs10490924 [P < 0.00088]和C3_rs2230199 [P < 0.00015])以及一个临床因素(对侧眼存在GA [P < 0.00023])。这些相关性共同解释了GA病变进展中高达7.2%的个体间差异,在旨在评估针对AMD所致晚期GA的新型治疗方案的干预性临床试验的策略规划中应予以考虑。