Retinal disease risk in electronic cigarette users versus combustible cigarette smokers: a retrospective cohort study

Purpose To compare age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO) between e-cigarette users and combustible cigarette smokers. Design Retrospective, propensity score-matched cohort study. Subjects, Participants, and/or Controls Using the TriNetX US Collaborative Network (67 healthcare organizations; >115 million patients), e-cigarette users and combustible cigarette smokers were identified by ICD-10-CM codes. Cohorts were matched 1:1 on 12 covariates, yielding 451,482 patients per group. A secondary non-advanced dry AMD cohort included 445,153 matched patients per group after excluding prior wet AMD. Methods, Intervention, or Testing Outcomes were assessed over 300 days. Risk ratios and time-to-event hazard ratios (HRs) with log-rank testing were calculated. Prespecified analyses included age ≥65 years, a never-smoker proxy comparison, and dry-to-wet AMD progression. Results E-cigarette use was not associated with significant differences in pooled AMD (HR 0.917), wet AMD (HR 0.875), or non-advanced dry AMD (HR 1.345). DR hazard was significantly lower for overall DR (HR 0.654), advanced DR (HR 0.692), and non-advanced DR (HR 0.738). RVO hazard was numerically higher but nonsignificant (HR 1.606). The never-smoker comparison suggested outcome-specific ascertainment bias. Combustible smokers with dry AMD progressed to wet AMD faster than never-smokers (HR 1.284). Conclusions E-cigarette use was not associated with significant AMD differences versus combustible smoking. DR hazard was lower, while RVO was numerically higher. Findings are hypothesis-generating given residual confounding and differential ascertainment.