Abstract
Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Ophthalmologica |
Vol/bind | 245 |
Udgave nummer | 5 |
Sider (fra-til) | 421-430 |
Antal sider | 10 |
ISSN | 0030-3755 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:The study was supported by the Rigshospitalet (grant E-23334-02), P. Carl Petersens Fond (grant 19102), Helsefonden (grant 19-B-0063), Aase og Ejnar Danielsens Fond (grant 18-10-0698), Beckett Fonden (grant 19-2-3490), Einar Willumsen Fonden (grant 500028), and Horizon 2020, the European Union’s Framework Programme for Research and Innovation, under grant agreement No. 780989 (MERLIN). JB was supported by the VELUX Foundation (grant 00028975). SPR was supported by the OPUS Foundation and the Alfred-Vogt Foundation. The funding organizations had no role in the design or conduct of this research.
Publisher Copyright:
© 2022 The Author(s). Published by S. Karger AG, Basel.