PURPOSE To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). DESIGN Retrospective analysis of a prospective cohort study. PARTICIPANTS Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. METHODS Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan-Meier analyses and multivariable proportional hazard regressions were performed. MAIN OUTCOME MEASURES Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. RESULTS Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98-2.82; P < 0.001); 67% of eyes progressed to late AMD 5 years after DPED detection. Drusenoid pigment epithelial detachment was associated with increased risk of ≥3 lines of VA loss (HR, 3.08; CI, 2.41-3.93; P < 0.001) with 46% of eyes experiencing vision loss at 5 years (with or without progression to late AMD). ARMS2 risk alleles (1 vs. 0: HR, 2.72, CI, 1.58-4.70; 2 vs. 0: HR, 3.16, CI, 1.60-6.21, P < 0.001) and increasing GRS group (4 vs. 1) (HR, 12.17, CI, 3.66-40.45, P < 0.001) were significantly associated with DPED development in AREDS. There were no significant genetic results in AREDS2. CONCLUSIONS This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

中文翻译：

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与年龄相关的黄斑变性相关的类胡萝卜素色素上皮分离的自然史：与年龄相关的眼病研究2报告第17号。

目的探讨与年龄相关性黄斑变性（AMD）相关的类疣性肾上腺素色素上皮脱离（DPED）的自然史和遗传关联。设计一项前瞻性队列研究的回顾性分析。参与者4203位年龄相关的眼病研究2（AREDS2）参与者中，有391眼（325名参与者）患有DPED，但在进行DPED检测时未出现晚期AMD。遗传分析包括120名白人AREDS2参与者和145名患有DPED的与年龄有关的眼疾研究（AREDS）参与者。方法对基线和年度立体眼底照片进行中央分级，以检测DPED（直径≥433μm的汇合的玻璃疣的清晰定义的黄色高丘），并评估晚期AMD的进展率：地理萎缩（GA）和新生血管（NV）- AMD。五个单核苷酸多态性（CFH [rs10611670]，研究了C3 [rs2230199]，CFI [rs10033900]，C2 / CFB [rs114254831]，ARMS2 [rs10490924]）和遗传风险评分（GRS）组与DPED发育的关系。进行了Kaplan-Meier分析和多变量比例风险回归。主要观察指标：从DPED检测开始，AMD晚期进展率和视敏度（VA）下降≥3线；DPED发育速度与基因型的相关性。结果DPED检测的平均随访时间（标准差[SD]）为4.7（0.9）年。DPED与晚期AMD进展的风险增加相关（危险比[HR]为2.36； 95％置信区间[CI]为1.98-2.82； P <0.001）；在检测到DPED后5年，有67％的眼睛进展到AMD晚期。类胡萝卜素色素上皮脱离与VA丢失≥3行的风险增加相关（HR，3。08; CI，2.41-3.93；P <0.001），其中46％的眼睛在5年内出现视力丧失（无论是否进展为晚期AMD）。ARMS2风险等位基因（1 vs. 0：HR，2.72，CI，1.58-4.70; 2 vs. 0：HR，3.16，CI，1.60-6.21，P <0.001）和GRS组增加（4 vs. 1）（HR （12.17，CI，3.66-40.45，P ＜0.001）与AREDS中DPED的发展显着相关。AREDS2没有明显的遗传结果。结论本研究重复了以前对DPED眼睛进行自然史研究的结果，包括进展为晚期AMD和视力丧失的高发生率（无论进展为晚期AMD）。遗传关联与与AMD进展相关的基因一致。ARMS2风险等位基因（1 vs. 0：HR，2.72，CI，1.58-4.70; 2 vs. 0：HR，3.16，CI，1.60-6.21，P <0.001）和GRS组增加（4 vs. 1）（HR （12.17，CI，3.66-40.45，P ＜0.001）与AREDS中DPED的发展显着相关。AREDS2没有明显的遗传结果。结论本研究重复了以前对DPED眼睛进行自然史研究的结果，包括进展为晚期AMD和视力丧失的高发生率（无论进展为晚期AMD）。遗传关联与与AMD进展相关的基因一致。ARMS2风险等位基因（1 vs. 0：HR，2.72，CI，1.58-4.70; 2 vs. 0：HR，3.16，CI，1.60-6.21，P <0.001）和GRS组增加（4 vs. 1）（HR （12.17，CI，3.66-40.45，P ＜0.001）与AREDS中DPED的发展显着相关。AREDS2没有明显的遗传结果。结论本研究重复了以前对DPED眼睛进行自然史研究的结果，包括进展为晚期AMD和视力丧失的高发生率（无论进展为晚期AMD）。遗传关联与与AMD进展相关的基因一致。AREDS2没有明显的遗传结果。结论本研究重复了以前对DPED眼睛进行自然史研究的结果，包括进展为晚期AMD和视力丧失的高发生率（无论进展为晚期AMD）。遗传关联与与AMD进展相关的基因一致。AREDS2没有明显的遗传结果。结论本研究重复了以前对DPED眼睛进行自然史研究的结果，包括进展为晚期AMD和视力丧失的高发生率（无论进展为晚期AMD）。遗传关联与与AMD进展相关的基因一致。