Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Cologne Image Reading Center, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Mol Vis. 2021 Dec 31;27:757-767. eCollection 2021.
The purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD).
This case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined.
RPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, rs2075650, rs10490924, rs800292, rs12144939, rs10033900, rs13081855, rs3812111, rs2049622, and rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886.
RPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.
本研究旨在分析伴有和不伴有年龄相关性黄斑变性（AMD）的患者中与网状假性drusen（RPD）相关的遗传和非遗传因素。
本病例对照研究纳入了来自前瞻性多中心欧洲遗传数据库（EUGENDA）的 2719 例连续患者。通过彩色眼底照片和光学相干断层扫描（OCT）评估 AMD 和 RPD 的存在。评估 RPD 与 39 种已知 AMD 多态性和各种非遗传危险因素的相关性。基于包含以下内容的广义线性模型（GLM）进行逐步向后变量选择：a）年龄、性别和遗传因素和 b）所有预测因子。确定接受者操作特征（ROC）曲线和曲线下面积（AUC）。
262 例存在 RPD（无 AMD，n=9[0.7%]；早期/中期 AMD，n=75[12.4%]；晚期 AMD，n=178[23.8%]）。包含年龄、rs2075650、rs10490924、rs800292、rs12144939、rs10033900、rs13081855、rs3812111、rs2049622 和 rs4296082 的遗传模型的 ROC 分析显示 AUC 为 0.871。考虑所有可能的预测因子，向后选择揭示了一组略有不同的遗传因素，以及以下非遗传危险因素：吸烟、类风湿性关节炎、类固醇、抗青光眼药物和过去的阳光暴露；结果显示 AUC 为 0.886。
RPD 与 AMD 具有多种遗传和非遗传危险因素。未来的 AMD 分级系统应将 RPD 作为一个重要的风险表型进行整合。
