Tobacco Exposure and Risk of Developing Fuchs Endothelial Corneal Dystrophy in the Women's Health Initiative Studies

Objective: We prospectively examined the association between tobacco exposure (personal/secondhand smoking [SHS]) and Fuchs endothelial corneal dystrophy (FECD) in older women, the group most impacted by FECD. Design: We conducted a secondary data analysis utilizing the Women's Health Initiative's (WHI's) Observational Study and Clinical Trials data. Participants: Postmenopausal women aged >65 who participated in WHI, had available Medicare claims data, and did not have FECD within 1 year after WHI enrollment were included (N = 37 824). Methods: Smoking status, pack-years, and average cigarettes per day were assessed at baseline (1993-1998). Secondhand smoking was assessed by location (childhood or adulthood at home and work). Participant characteristics were compared by personal smoking history and SHS status. Crude and adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of FECD by personal smoking exposure and by SHS status. Main Outcome Measures: Incident FECD cases were identified objectively via Medicare claims data through 2019. Results: Current smokers compared with never smokers were more likely to be younger, have lower body mass indices, and were less likely to be White, married, and users of hormone replacement therapy. Current smokers had an increased risk of FECD compared with never smokers (HR = 1.12, CIs: 0.90–1.38) and former smokers had a slight decreased risk of FECD compared with never smokers (HR = 0.92, CIs: 0.84–1.01). Current smokers who smoked ≥15 cigarettes/day had a 26.0% (HR = 1.26, CIs: 0.94–1.68) greater risk of developing FECD compared with never smokers. However, former smokers who smoked ≥15 cigarettes/day had a 14.0% (HR = 0.86, CIs: 0.76–0.97) reduced risk of developing FECD compared with never smokers. Most women (93.6%) were exposed to SHS sometime in their life. Never smokers exposed to SHS at home during childhood or adulthood had approximately a 22%-25% nonsignificant increased risk of developing FECD compared with never smokers without SHS exposure. Conclusions: In this sample of postmenopausal women, personal smoking and SHS were not significantly associated with increased risk of FECD, but suggestions of an increased risk were observed in current smokers. Our findings may have been impacted by lack of variation in exposures, survival, and sick-quitter biases. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.