Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
The Emmes Corporation, Rockville, Maryland.
Ophthalmology. 2019 Feb;126(2):261-273. doi: 10.1016/j.ophtha.2018.08.017. Epub 2018 Aug 22.
To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD).
Retrospective analysis of a prospective cohort study.
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.
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.
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.
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.
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.
研究与年龄相关性黄斑变性（AMD）相关的玻璃膜疣性色素上皮脱离（DPED）的自然史和遗传相关性。
前瞻性队列研究的回顾性分析。
在年龄相关性眼病研究 2 期（AREDS2）的 4203 名参与者中，有 391 只眼（325 名参与者）在 DPED 检测时出现 DPED 且无晚期 AMD。遗传分析包括 120 名白种人 AREDS2 参与者和 145 名患有 DPED 的年龄相关性眼病研究（AREDS）参与者。
使用基线和每年的立体眼底照片进行中心分级，以检测 DPED，即直径≥433μm 的融合性玻璃膜疣的明确黄色隆起丘；并评估向晚期 AMD（地图样萎缩和新生血管性 AMD）进展的速度。研究了 5 个单核苷酸多态性（CFH[rs10611670]、C3[rs2230199]、CFI[rs10033900]、C2/CFB[rs114254831]、ARMS2[rs10490924]）和遗传风险评分（GRS）组与 DPED 发展的关联。进行了 Kaplan-Meier 分析和多变量比例风险回归。
向晚期 AMD 进展的速度和 DPED 检测后视力（VA）下降≥3 行的速度；DPED 发展速度与基因型的关系。
从 DPED 检测到的平均（标准差）随访时间为 4.7（0.9）年。DPED 与向晚期 AMD 进展的风险增加相关（风险比[HR]，2.36；95%置信区间[CI]，1.98-2.82；P<0.001）；67%的眼在 DPED 检测后 5 年内进展为晚期 AMD。DPED 与 VA 丧失≥3 行的风险增加相关（HR，3.08；CI，2.41-3.93；P<0.001），46%的眼在 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 比 0：HR，2.72；CI，1.58-4.70；2 比 0：HR，3.16；CI，1.60-6.21；P<0.001）和增加的 GRS 组（4 比 1：HR，12.17；CI，3.66-40.45；P<0.001）与 AREDS 中的 DPED 发展显著相关。在 AREDS2 中没有发现显著的遗传结果。
本研究复制了先前 DPED 眼的自然史研究结果，包括向晚期 AMD 和视力丧失（无论是否向晚期 AMD 进展）的高进展速度。遗传相关性与与 AMD 进展相关的基因一致。
