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雌激素暴露指标与富克斯内皮性角膜营养不良严重程度之间的关联。

Associations between measures of oestrogen exposure and severity of Fuchs endothelial corneal dystrophy.

作者信息

Petrela Redion B, Chhetri Chandra Divyash, Najafi Ahmad, Zhang Zhaoqi, A Rinkoski Tommy, Wieben Eric D, Fautsch Michael P, Chakraborty Saptarshi, E Millen Amy, Patel Sangita P

机构信息

Ophthalmology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.

Biostatistics, University at Buffalo, Buffalo, New York, USA.

出版信息

BMJ Open Ophthalmol. 2025 May 14;10(1):e001884. doi: 10.1136/bmjophth-2024-001884.

Abstract

AIMS

To determine the associations between measures of oestrogen exposure and Fuchs endothelial corneal dystrophy (FECD) severity.

METHODS

Clinic-based cross-sectional study of 32 postmenopausal women and 11 men with mild or severe FECD, age>55 years. Participants completed questionnaires for data on demographics, anthropometric factors, medical history and potential risk factors for FECD. Women completed an additional reproductive history questionnaire used to calculate the months of lifetime oestrogen exposure. Slit-lamp biomicroscopy, specular microscopy, corneal Scheimpflug tomography and laboratory testing ( repeat expansion quantification, total estradiol, free estradiol, sex hormone binding globulin (SHBG), calcaneal bone density) were performed. Logistic regression models were developed to predict FECD severity based on three-way interactions of each oestrogen exposure measure, sex and genotype.

RESULTS

43 patients were enrolled in the study (mild FECD: 17 women, 3 men; severe FECD: 15 women, 8 men). Serum-free estradiol was higher in the severe compared with mild FECD group (0.21±0.2 vs 0.09±0.1 pg/mL; p=0.046). When stratified by sex, men showed no significant associations between oestrogen measures and FECD severity. However, in women, the odds of severe FECD were increased with more months of lifetime oestrogen exposure (all women; log OR (95% credible interval): 1.3 (0.14 to 4.3)), higher concentrations of free estradiol (all women; 2.1 (0.0049 to 10)), greater % free estradiol (only women without repeat expansion; 1.3 (0.16 to 3.8)) and higher concentrations of SHBG (only women with repeat expansion; 2.2 (0.45 to 9.1)).

CONCLUSIONS

While the application of these data is constrained by the limited number of participants, a clinic-based sample, small number of men compared with women and single-point measures of serum hormone measures, these data suggest that FECD severity is associated with higher oestrogen exposures in women but not men and may be dependent on repeat expansion status.

摘要

目的

确定雌激素暴露指标与富克斯内皮性角膜营养不良(FECD)严重程度之间的关联。

方法

对32名绝经后女性和11名年龄大于55岁的轻度或重度FECD男性进行基于诊所的横断面研究。参与者完成问卷调查,以获取人口统计学、人体测量因素、病史和FECD潜在风险因素的数据。女性还完成了一份额外的生殖史问卷,用于计算终生雌激素暴露月数。进行了裂隙灯生物显微镜检查、镜面显微镜检查、角膜全景断层扫描和实验室检测(重复扩增定量、总雌二醇、游离雌二醇、性激素结合球蛋白(SHBG)、跟骨骨密度)。建立逻辑回归模型,以基于每种雌激素暴露指标、性别和基因型的三向相互作用预测FECD严重程度。

结果

43名患者纳入研究(轻度FECD:17名女性,3名男性;重度FECD:15名女性,8名男性)。重度FECD组的血清游离雌二醇高于轻度FECD组(0.21±0.2对0.09±0.1 pg/mL;p = 0.046)。按性别分层时,男性的雌激素指标与FECD严重程度之间无显著关联。然而,在女性中,终生雌激素暴露月数越多、游离雌二醇浓度越高、游离雌二醇百分比越高(仅无重复扩增的女性)和SHBG浓度越高(仅患有重复扩增的女性),患重度FECD的几率增加(所有女性;对数比值比(95%可信区间):1.3(0.14至4.3))、2.1(0.0049至10)、1.3(0.16至3.8)和2.2(0.45至9.1))。

结论

虽然这些数据的应用受到参与者数量有限、基于诊所的样本、男性与女性数量较少以及血清激素指标单点测量的限制,但这些数据表明,FECD严重程度与女性而非男性的较高雌激素暴露有关,并且可能取决于重复扩增状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5dae/12083347/3efbee23157d/bmjophth-10-1-g001.jpg

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