Editorial: Disentangling the Impact of Reticular Pseudodrusen Phenotype and the ARMS2/HTRA1 Risk Allele in Geographic Atrophy: The AREDS 2 Study Report 32
本文探討了在AREDS 2研究中reticular pseudodrusen (RPD)與ARMS2 / HTRA1 risk allele對geographic atrophy(GA)的影響，並證實了具有RPD和ARMS2風險等位基因的眼睛的GA生長速度比沒有它們的眼睛更快。通過中介分析，本研究顯示RPD的存在不會介導ARMS2基因型和GA生長之間的聯繫。此研究對於揭示GA進展的遺傳和臨床風險因素的作用有重要意義，並提示在GA的治療試驗中，需要考慮ARMS2和RPD狀態以提高其精度和功效。然而，該研究也存在一些限制，例如使用FAF而不是更敏感的技術來確定RPD狀態。總體而言，該研究是針對解開RPD狀態和ARMS2基因型對GA進展影響的一個重要進展，並對臨床實踐和臨床試驗產生了重要影響。
The article discusses the results of a post hoc analysis of 771 eyes with geographic atrophy (GA) from the Age-Related Eye Disease Study 2, which aimed to determine the impact of reticular pseudodrusen (RPD) phenotype and ARMS2 or HTRA1 risk allele presence, or both, on GA progression. The analysis confirmed that GA growth was significantly faster in eyes with RPD and in individuals carrying the ARMS2 risk alleles, and that RPD presence was associated with faster progression to the central macula in noncentral GA. However, the authors found that RPD does not mediate the association between ARMS2 genotype and GA growth, suggesting that these two risk factors influence GA via potentially independent mechanisms. The study has important implications for clinical trials of GA, and the authors suggest that ARMS2 and RPD status should be considered during patient selection and randomization to increase the precision and power of these trials. The study is also an important step toward dissecting the roles of genetic and clinical risk factors in GA progression, and the findings suggest that RPD phenotype and ARMS2 or HTRA1 genotype are likely contributing via distinct mechanisms.