Observational studyBMJ open ophthalmology2026
Sustained proton-pump inhibitor exposure and incident age-related macular degeneration: a new-user, population-based cohort study.
Observational study in BMJ open ophthalmology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveProton-pump inhibitors (PPIs) may disrupt lysosomal acidification, a pathway implicated in age-related macular degeneration (AMD) pathogenesis. We evaluated whether sustained PPI exposure increased the risk of incident AMD in older adults aged ≥60 years. METHODS AND ANALYSIS: This retrospective observational cohort study included adults aged ≥60 years with sustained PPI exposure, matched 1:1 to unexposed controls on demographics, overall health, healthcare utilisation, cardiometabolic factors. Participants were identified from electronic health records. Sustained PPI exposure was defined as ≥2 years of cumulative use within 3 years of the first prescription. Fine-Gray models treating death as a competing event estimated subdistribution hazard ratios (sHRs) for AMD within 10 years; cause-specific Cox models provided complementary HRs. Analyses included histamine H2-receptor antagonists (H2-antagonists) as a negative exposure control and active comparator.
resultsIncident AMD occurred in 814/49 796 PPI exposed participants (1.64%) and 668/49 796 controls (1.34%) (overall sHR=1.24, 95% CI 1.12 to 1.38; p<0.001; HR=1.25, 95% CI 1.13 to 1.38, p<0.001). Proportional sHRs were non-constant; sHRs were 1.09 (95% CI 0.91 to 1.29) before 2.5 years and 1.33 (95% CI 1.17 to 1.51) thereafter. For non-exudative AMD, 640 PPI exposed (1.29%) and 510 unexposed (1.02%) participants developed disease (overall sHR=1.28, 95% CI 1.14 to 1.44; p<0.001, HR=1.29, 95% CI 1.14 to 1.44, p<0.001). Among those with non-exudative AMD, 190/2503 PPI-exposed participants (7.59%) and 179/2503 controls (7.15%) progressed to exudative AMD (sHR and HR=1.03, 95% CI 0.84 to 1.26; p=0.802 and p=0.801, respectively). No association was observed between H2-antagonists and AMD (sHR=1.02, 95% CI 0.88 to 1.19; p=0.784; HR=1.03, 95% CI 0.88 to 1.20, p=0.729). Results were consistent in the active-comparator analysis (reciprocal overall sHR=1.24, 95% CI 1.04 to 1.48; p=0.016; HR=1.25, 95% CI 1.05 to 1.49, p=0.012).
conclusionSustained PPI exposure was associated with a modestly higher AMD risk, whereas no association was observed with H2-antagonists. The consistency of the active-comparator findings supports the potential specificity of this association and warrants further investigation to determine its clinical implications.
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