Reticular Pseudodrusen Status, ARMS2/HTRA1 Genotype, and Geographic Atrophy Enlargement

Ophthalmology Volume 130, Number 5, May 2023

中文摘要

本研究旨在探討網狀偽黃斑病變(reticular pseudodrusen, RPD)狀態、ARMS2/HTRA1基因型或兩者是否與地理性黃斑退化(geographic atrophy, GA)擴大速率有關，並分析RPD狀態對基因效應的可能調節作用。結果顯示，RPD狀態並未調節ARMS2/HTRA1基因型與更快擴大之間的關聯。RPD的存在和ARMS2/HTRA1基因型相對獨立的風險因素，運作的機制也不同。對GA擴大速率的準確預測對臨床試驗的有效性和精準度至關重要。就此問題進行研究可以明確是否需要進行基因測試以達到最佳的準確性，或者僅需用影像特徵（包括RPD狀態）即可。研究還發現GA的擴大在有RPD的眼睛中明顯更快。然而，儘管ARMS2風險等位基因與RPD的存在有關，而RPD的存在又與GA的快速擴大有關，但透過RPD狀態的這種間接關係似乎並未產生任何顯著的影響。

English Abstract

This study aimed to determine whether the status of reticular pseudodrusen (RPD), the ARMS2/HTRA1 genotype, or both are associated with the enlargement rate of geographic atrophy (GA) and to analyze any potential mediation of genetic effects by RPD status. The findings showed that RPD status does not mediate the association between the ARMS2/HTRA1 genotype and faster enlargement. The presence of reticular pseudodrusen and the ARMS2/HTRA1 genotype are relatively independent risk factors, operating by distinct mechanisms. Accurate predictions of the GA enlargement rate are crucial for the power and precision of clinical trials. Addressing these questions should clarify whether genetic testing would be required for optimal accuracy or whether imaging features (including RPD status) would suffice. The study also found that GA enlargement is significantly faster in eyes with RPD. However, despite the fact that ARMS2 risk alleles are associated with RPD presence, which in turn is associated with faster GA enlargement, this potential indirect relationship via RPD status does not seem to make any meaningful contribution.