Bak Marie, Sørensen Torben Lykke, Flachs Esben Meulengracht, Zwisler Ann-Dorthe, Juel Knud, Frederiksen Henrik, Hasselbalch Hans Carl
Department of Haematology, Zealand University Hospital, University of Copenhagen, Roskilde, Denmark.
Department of Ophthalmology, Zealand University Hospital, University of Copenhagen, Roskilde, Denmark.
JAMA Ophthalmol. 2017 Aug 1;135(8):835-843. doi: 10.1001/jamaophthalmol.2017.2011.
It has been suggested that systemic inflammation increases the risk of age-related macular degeneration (AMD). Given that chronic immune modulation is present in patients with myeloproliferative neoplasms (MPNs), the risk of AMD in these patients may be increased.
To compare the risk of AMD in patients with MPNs with the risk of AMD in matched controls from the general population.
DESIGN, SETTING, AND PARTICIPANTS: A nationwide population-based cohort study using Danish registers was conducted of all patients in Denmark who received a diagnosis between January 1, 1994, and December 31, 2013, of essential thrombocythemia, polycythemia vera, myelofibrosis, or unclassifiable MPNs. For each patient, 10 age- and sex-matched controls were included. All patients without prior AMD were followed up from the date of diagnosis (or corresponding entry date for the controls) until the first AMD diagnosis, death or emigration, or December 31, 2013, whichever occurred first. Data analysis was performed from April 1, 2015, to October 31, 2016.
Incidence of AMD recorded in specialized hospital-based care. The rates and absolute risk of AMD were calculated. Using Cox proportional hazards regression models, smoking and risk-time adjusted hazard ratios (HRs) between patients and controls were calculated. In addition, HRs of neovascular AMD after 2006 were calculated since antivascular endothelial growth factor treatment was introduced nationwide at hospitals thereafter.
A total of 7958 patients with MPNs (4279 women [53.8%] and 3679 men [46.2%]; mean [SD] age at diagnosis, 66.4 [14.3] years) were included in the study. The rate of AMD per 1000 person-years at risk was 5.2 (95% CI, 4.6-5.9) for patients with MPNs (2628 with essential thrombocythemia, 3063 with polycythemia vera, 547 with myelofibrosis, and 1720 with unclassifiable MPNs) and 4.3 (95% CI, 4.1-4.4) for the 77 445 controls, while the 10-year risk of AMD was 2.4% (95% CI, 2.1%-2.8%) for patients with MPNs and 2.3% (95% CI, 2.2%-2.4%) for the controls. The risk of AMD was increased overall for patients with MPNs (adjusted HR, 1.3; 95% CI, 1.1-1.5), with adjusted HRs for the subtypes of 1.2 (95% CI, 1.0-1.6) for essential thrombocythemia, 1.4 (95% CI, 1.2-1.7) for polycythemia vera, 1.7 (95% CI, 0.8-4.0) for myelofibrosis, and 1.5 (95% CI, 1.1-2.1) for unclassifiable MPNs. In addition, patients with MPNs had a higher risk of neovascular AMD (adjusted HR, 1.4; 95% CI, 1.2-1.6).
Our results suggest that patients with MPNs are at increased risk of AMD, supporting the possibility that systemic inflammation is involved in the pathogenesis of AMD.
有人提出全身炎症会增加年龄相关性黄斑变性（AMD）的风险。鉴于骨髓增殖性肿瘤（MPN）患者存在慢性免疫调节，这些患者患AMD的风险可能会增加。
比较MPN患者患AMD的风险与来自普通人群的匹配对照者患AMD的风险。
设计、设置和参与者：利用丹麦登记册进行了一项全国性的基于人群的队列研究，纳入了1994年1月1日至2013年12月31日期间在丹麦被诊断为原发性血小板增多症、真性红细胞增多症、骨髓纤维化或无法分类的MPN的所有患者。为每位患者纳入10名年龄和性别匹配的对照者。所有无既往AMD的患者从诊断日期（或对照者的相应入组日期）开始随访，直至首次诊断为AMD、死亡或移民，或2013年12月31日，以先发生者为准。数据分析于2015年4月1日至2016年10月31日进行。
在专门的医院护理中记录的AMD发病率。计算AMD的发生率和绝对风险。使用Cox比例风险回归模型，计算患者与对照者之间经吸烟和风险时间调整后的风险比（HR）。此外，计算2006年后新生血管性AMD的HR，因为此后全国医院引入了抗血管内皮生长因子治疗。
该研究共纳入7958例MPN患者（4279例女性[53.8%]和3679例男性[46.2%]；诊断时的平均[标准差]年龄为66.4[14.3]岁）。MPN患者每1000人年的风险中AMD发生率为5.2（95%CI，4.6 - 5.9）（2628例原发性血小板增多症患者、3063例真性红细胞增多症患者、547例骨髓纤维化患者和1720例无法分类的MPN患者），77445名对照者为4.3（95%CI，4.1 - 4.4），而MPN患者的10年AMD风险为2.4%（95%CI，2.1% - 2.8%），对照者为2.3%（95%CI，2.2% - 2.4%）。MPN患者总体患AMD的风险增加（调整后HR，1.3；95%CI，1.1 - 1.5），各亚型的调整后HR分别为：原发性血小板增多症1.2（95%CI，1.0 - 1.6）、真性红细胞增多症1.4（95%CI，1.2 - 1.7）、骨髓纤维化1.7（95%CI，0.8 - 4.0）、无法分类的MPN 1.5（95%CI，1.1 - 2.1）。此外，MPN患者患新生血管性AMD的风险更高（调整后HR，1.4；95%CI，1.2 - 1.6）。
我们的结果表明，MPN患者患AMD的风险增加，支持全身炎症参与AMD发病机制的可能性。
