年轻人阻塞性睡眠呼吸暂停与圆锥角膜之间的双向关联：一项多中心回顾性队列研究

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中文摘要

目的： 采用匹配队列设计评估年轻人中阻塞性睡眠呼吸暂停（OSA）与圆锥角膜（KC）之间的双向关联。
方法： 使用TriNetX研究网络进行的多中心回顾性队列研究。在正向分析中，将18至45岁、患有OSA（ICD-10：G47.33）且有多导睡眠监测证据的成人，与3个倾向评分匹配的对照进行比较：接受多导睡眠监测评估的对照（有无年龄限制）以及一般就诊对照。在反向分析中，将患有KC且有角膜影像学证据（H18.6并接受角膜地形图、前段OCT或角膜测厚检查）的患者，与3个平行队列进行比较。比较采用1:1倾向评分匹配（卡钳值0.2），匹配变量包括人口学特征、体重指数分层、特应性/代谢性合并症以及医疗资源利用情况。在5年和10年时估计风险比（HR）。急性阑尾炎在所有比较中作为预先设定的阴性对照结局；在一般就诊对照中还额外评估了嵌甲。
结果： 正向主要分析每组匹配了48,954例患者。新发KC的5年HR为2.01（95% CI：1.21-3.32；P = 0.006），10年时保持稳定（HR：2.03，1.28-3.21），敏感性分析HR分别为1.72和1.88，结果一致。反向主要分析每组匹配了4350例患者。新发OSA的5年HR无统计学意义（HR：1.13，0.91-1.40）；10年HR为1.29（1.07-1.55；P = 0.008）。阴性对照在所有主要比较中均为阴性。正向主要HR的E值为3.45。
结论： 在调整已测量的混杂因素后，有多导睡眠监测证据的OSA与新发KC相关。反向分析显示关联较弱且存在时间延迟，鉴于检测偏倚，需谨慎解读。这些发现支持对疑似角膜扩张性疾病的年轻成人考虑进行睡眠评估；但这些发现并未说明治疗OSA是否会改变已确诊KC的进展。

英文摘要

PURPOSE: To evaluate the bidirectional association between obstructive sleep apnea (OSA) and keratoconus (KC) in young adults using matched-cohort designs.
METHODS: Multicenter retrospective cohort study using the TriNetX Research Network. In the forward direction, adults aged 18 to 45 with OSA (ICD-10: G47.33) and evidence of polysomnography were compared with 3 propensity-score-matched comparators: polysomnography-evaluated controls, with and without age restriction, and a general encounter control. In the reverse direction, patients with KC and evidence of corneal imaging (H18.6 with topography, anterior segment OCT, or pachymetry) were compared with 3 parallel cohorts. Comparisons used 1:1 propensity-score matching (caliper 0.2) on demographics, body mass index strata, atopic/metabolic comorbidities, and health care utilization. Hazard ratios (HRs) were estimated at 5 and 10 years. Acute appendicitis served as the prespecified negative control outcome in all comparisons; ingrown nail was additionally evaluated in the general encounter comparator.
RESULTS: The forward primary analysis matched 48,954 patients per arm. The 5-year HR for incident KC was 2.01 (95% CI: 1.21-3.32; P = 0.006), stable at 10 years (HR: 2.03, 1.28-3.21), with concordant sensitivity HRs of 1.72 and 1.88. The reverse primary analysis matched 4350 patients per arm. The 5-year HR for incident OSA was nonsignificant (HR: 1.13, 0.91-1.40); the 10-year HR was 1.29 (1.07-1.55; P = 0.008). The negative control was null in all primary comparisons. The E-value for the forward primary HR was 3.45.
CONCLUSIONS: OSA with evidence of polysomnography was associated with incident KC after adjustment for measured confounders. The reverse direction showed a weaker, time-delayed association requiring cautious interpretation given detection bias. These findings support consideration of sleep evaluation in young adults with suspected corneal ectatic disease; they do not address whether treating OSA alters progression in established KC.