Supplementary Material for: Long-Term Trends in the Global Burden of Age-Related Macular Degeneration: Sex Differences, Aging Effects, and Future Projections in Middle-Aged and Older Adults

Background: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in middle-aged and older populations worldwide. Understanding its long-term epidemiological trends is essential for anticipating future healthcare needs and guiding preventive strategies. This study characterizes the global, regional, and national burden of AMD in adults aged ≥45 years, with a focus on sex disparities, aging effects, and projected trends Methods: Using data from the Global Burden of Disease Study 2021, we analyzed the prevalence and disability-adjusted life years (DALYs) of AMD across age, sex, region, country, and Socio-Demographic Index (SDI) groups. We applied an Age-Period-Cohort (APC) model to disentangle the effects of aging, temporal changes, and birth cohort on AMD risk. Frontier analysis was conducted to identify best-practice benchmarks in disease burden reduction. The association between SDI and AMD burden was assessed to evaluate health inequities. An Autoregressive Integrated Moving Average (ARIMA) model was used to project age-standardized DALY rates (ASDR) and prevalence rates (ASPR) from 2022 to 2036. Results: Between 1990 and 2021, the absolute number of AMD cases and DALYs nearly doubled. In 2021, both prevalence and DALY rates increased exponentially with age, with females exhibiting consistently higher rates across all age groups. The APC model indicated a declining trend in AMD risk over successive birth cohorts, suggesting potential improvements in early-life or cumulative risk factors. Notably, the highest age-standardized rates were observed in low-SDI regions, highlighting significant global inequities in disease burden. ARIMA projections suggest a modest but concerning increase in the global ASDR, rising to 6.80 (95% CI: 5.82-7.78) by 2036, with female ASDR reaching 7.46 (95% CI: 6.29-8.63). Conclusions: The burden of AMD remains substantial and is projected to grow, particularly among aging populations and in low-resource settings. The persistent sex disparity, especially the elevated burden in elderly women, calls for targeted screening and intervention programs. These findings emphasize the need for equitable, age- and sex-sensitive public health strategies to mitigate the rising impact of AMD in the coming decades.

背景：年龄相关性黄斑变性（Age-related macular degeneration, AMD）是全球中老年人群不可逆视力丧失的主要病因。明确其长期流行病学趋势，对于预判未来医疗需求、指导疾病预防策略至关重要。本研究旨在系统阐明45岁及以上成人AMD在全球、区域及国家层面的疾病负担，重点关注性别差异、衰老效应及未来发展趋势。方法：本研究依托2021年全球疾病负担研究（Global Burden of Disease Study 2021）的数据，分析了不同年龄、性别、区域、国家及社会人口指数（Socio-Demographic Index, SDI）分组下AMD的患病率与伤残调整寿命年（disability-adjusted life years, DALYs）。我们采用年龄-时期-队列（Age-Period-Cohort, APC）模型，分离衰老、时间变化及出生队列对AMD发病风险的影响效应。通过前沿分析确定疾病负担降低的最佳实践基准；评估SDI与AMD疾病负担的关联，以解析健康公平性问题。采用自回归积分滑动平均（Autoregressive Integrated Moving Average, ARIMA）模型，预测2022至2036年的年龄标准化伤残调整寿命年率（age-standardized DALY rate, ASDR）与年龄标准化患病率（age-standardized prevalence rate, ASPR）。结果：1990年至2021年间，AMD的绝对患病人数与DALYs总量近乎翻倍。2021年，AMD患病率与DALY率均随年龄呈指数级增长，且各年龄组女性的相关指标均持续高于男性。APC模型分析显示，后续出生队列的AMD发病风险呈逐步下降趋势，提示早年或累积性风险因素或已得到改善。值得注意的是，低SDI区域的年龄标准化率最高，凸显了全球疾病负担分布的显著不公平性。ARIMA模型预测结果表明，全球年龄标准化DALY率将出现小幅但值得警惕的增长，至2036年将升至6.80（95% CI：5.82-7.78），女性年龄标准化DALY率将达到7.46（95% CI：6.29-8.63）。结论：AMD的疾病负担依然沉重，且预计将持续攀升，尤其在老龄化人群与低资源地区。持续存在的性别差异，尤其是老年女性更高的疾病负担，呼吁开展针对性的筛查与干预项目。本研究结果强调，亟需制定公平、兼顾年龄与性别敏感性的公共卫生策略，以减轻未来数十年AMD带来的日益严重的影响。