{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T06:24:08Z","timestamp":1787293448632,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The pathogenesis of maculopathy remains incompletely understood, and emerging evidence implicates the gut\u2013eye axis in retinal and macular diseases. Given that antibiotics with anti-anaerobic activity may disrupt gut microbial ecology, this study investigated their association with the risk of incident maculopathy. We conducted a nationwide population-based study using the National Health Insurance Service\u2013National Sample Cohort of South Korea. A retrospective cohort study was used to assess cumulative systemic anaerobic antibiotic exposure during a 5-year baseline period and subsequent incident maculopathy from 2007 to 2019. After 1:1 propensity score matching, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. A nested case-control study was also conducted using risk-set sampling and 1:10 propensity score matching. Anaerobic antibiotic exposure during the 365 days before the index date was assessed, and odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression. Duration-response relationships were evaluated using formal trend analyses. Sensitivity analyses included age restriction, Fine-Gray competing risk models, extended exposure assessment windows, lag-time analyses, and a negative control comparator analysis using first-generation cephalosporins. In the retrospective cohort study, 326,436 anaerobic antibiotic users were matched to 326,436 non-users. Anaerobic antibiotic use was associated with an increased risk of incident maculopathy in the fully adjusted model (HR, 1.07; 95% CI, 1.03\u20131.12), with a significant duration-response trend and the highest risk observed for \u226557 days of cumulative use (HR, 1.24; 95% CI, 1.09\u20131.42). In the nested case-control study, 55,776 cases were matched to 557,760 controls. Anaerobic antibiotic use within 365 days before the index date was associated with increased odds of maculopathy (OR, 1.04; 95% CI, 1.02\u20131.07), also showing a significant duration-response trend. Sensitivity analyses and first-generation cephalosporin comparator analyses, generally supported the robustness of the findings. Systemic exposure to antibiotics with anti-anaerobic activity was associated with an increased risk of incident maculopathy, with a duration-response pattern across cumulative exposure categories. These findings suggest further investigation into gut microbiome disruption and the gut-eye axis as potential pathways involved in maculopathy.<\/jats:p>","DOI":"10.3389\/fphar.2026.1840229","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:35:36Z","timestamp":1787290536000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anaerobic antibiotic exposure and risk of maculopathy: a nationwide dual design study"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiyeon","family":"Park","sequence":"first","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University-ERICA Campus","place":["Ansan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghyun","family":"Cheon","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University-ERICA Campus","place":["Ansan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Seon","family":"Choi","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University-ERICA Campus","place":["Ansan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pre-Medicine, College of Medicine and Biostatistics Laboratory, Medical Research Collaborating Center, Hanyang University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Joon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, Hanyang University Hospital, Hanyang University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee-Eun","family":"Chung","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University-ERICA Campus","place":["Ansan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11349","DOI":"10.4088\/JCP.20f13681","article-title":"Mean difference, standardized mean difference (SMD), and their use in meta-analysis: as simple as it gets","volume":"81","author":"Andrade","year":"2020","journal-title":"J. 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