Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
Ophthalmologica. 2022;245(5):421-430. doi: 10.1159/000525652. Epub 2022 Jul 25.
The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 μm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort.
Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 μm, or (4) ≥20 small hard drusen combined with drusen ≥63 μm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects.
Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 μm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 μm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 μm at follow-up (p = 0.02). Development of drusen ≥63 μm was attributable to 49% genetic effects and 51% environmental effects.
The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 μm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 μm at baseline was associated with incident drusen ≥63 μm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking.
从正常眼底到早期（≥20 个小硬性玻璃膜疣）再到年龄相关性黄斑变性（AMD）的转变形式为直径≥63μm 的玻璃膜疣，这一点很有意思，因为小硬性玻璃膜疣可能是大玻璃膜疣的前兆。对 AMD 前体病变的研究可能为引发 AMD 的因素提供有价值的见解。在此，我们在一个基于人群的双胞胎队列中，对 20 年内玻璃膜疣的进展进行了研究。
对 138 对双胞胎进行了单中心、20 年的随访，包括生物测量、眼底光学相干断层扫描和眼底照相。将黄斑特征按每只眼分为（1）<20 个小硬性玻璃膜疣，（2）≥20 个小硬性玻璃膜疣，（3）玻璃膜疣≥63μm，或（4）≥20 个小硬性玻璃膜疣合并玻璃膜疣≥63μm。采用经典的易感性阈值方法和具有随机效应的多基因建模的双变量双分位模型分析了加性和显性遗传效应以及共享和非共享环境效应。
中位参与者年龄为 59 岁（范围 41-66 岁）。在 25 例（18%）新发黄斑玻璃膜疣病例中，7 例有≥20 个小硬性玻璃膜疣，18 例有玻璃膜疣≥63μm，而没有一例同时出现这两种病变。吸烟与新发≥20 个小硬性玻璃膜疣（p=0.04）和新发玻璃膜疣≥63μm（p=0.003）相关。基线时有≥20 个小硬性玻璃膜疣与随访时发生玻璃膜疣≥63μm相关（p=0.02）。玻璃膜疣≥63μm的发展归因于 49%的遗传效应和 51%的环境效应。
从每只眼 0 到 19 个小硬性黄斑玻璃膜疣进展到每只眼有≥20 个小硬性玻璃膜疣或玻璃膜疣≥63μm的风险与吸烟和遗传易感性有关。基线时无玻璃膜疣≥63μm但有≥20 个小硬性玻璃膜疣与 20 年后检查时发生玻璃膜疣≥63μm有关。该研究证实，小硬性黄斑玻璃膜疣是 AMD 的先兆，而避免吸烟可能会阻碍 AMD 的进展。
