Risk of retinal detachment and exposure to fluoroquinolones, common antibiotics, and febrile illness using a self-controlled case series study design: Retrospective analyses of three large healthcare databases in the US

PLoS One. 2022 Oct 6;17(10):e0275796. doi: 10.1371/journal.pone.0275796. eCollection 2022.

Abstract

Objective: The risk of retinal detachment (RD) following exposure to fluoroquinolone (FQ) has been assessed in multiple studies, however, results have been mixed. This study was designed to estimate the risk of RD following exposure to FQ, other common antibiotics, and febrile illness not treated with antibiotics (FINTA) using a self-controlled case series (SCCS) study design to reduce risk of confounding from unreported patient characteristics.

Design: Retrospective database analysis-SCCS.

Setting: Primary and Secondary Care.

Study population: 40,981 patients across 3 US claims databases (IBM® MarketScan® commercial and Medicare databases, Optum Clinformatics).

Outcome: RD.

Methods: Exposures included FQ as a class of drugs, amoxicillin, azithromycin, trimethoprim with and without sulfamethoxazole, and FINTA. For the primary analysis, all drug formulations were included. For the post hoc sensitivity analyses, only oral tablets were included. Risk windows were defined as exposure period (or FINTA duration) plus 30 days. Patients of all ages with RD and exposures in 3 US claims databases between 2012 to 2017 were included. Diagnostics included p value calibration and pre-exposure outcome analyses. Incidence rate ratios (IRR) and 95% confidence interval (CI) comparing risk window time with other time were calculated.

Results: Our primary analysis showed an increased risk for RD in the 30 days prior to exposure to FQ or trimethoprim without sulfamethoxazole. This risk decreased but remained elevated for 30 days following first exposure. Our post-hoc analysis, which excluded ophthalmic drops, showed no increased risk for RD at any time, with FQ and other antibiotics.

Conclusion: Our results did not suggest an association between FQ and RD. Oral FQ was not associated with an increased risk for RD during the pre- or post-exposure period.

Trial registration: ClinicalTrials.gov identifier: NCT03479736-March 21, 2018.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amoxicillin
  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin
  • Delivery of Health Care
  • Fluoroquinolones* / therapeutic use
  • Humans
  • Medicare
  • Retinal Detachment* / chemically induced
  • Retinal Detachment* / epidemiology
  • Retrospective Studies
  • Sulfamethoxazole
  • Trimethoprim
  • United States / epidemiology

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Amoxicillin
  • Azithromycin
  • Trimethoprim
  • Sulfamethoxazole

Associated data

  • ClinicalTrials.gov/NCT03479736

Grants and funding

This study was supported by Janssen Research & Development, LLC, who provided financial support for the work in the form of salaries for all the authors, and its commitment to pay the associated publishing fees. Janssen Research & Development, LLC’s Standard Operating Procedures require publication of studies that, like this one, concern its products and were intended for publication when they were begun. For the present study, that intention is documented by its registration with ClinicalTrails.gov. The funding organization’s Standard Operating Procedures also require that the study undergo a standard internal company review before it is submitted for publication. Internal company review is limited to roles not responsible for sales or marketing functions. Janssen Research & Development, LLC. did not have any additional role in the study design, data collection, analysis, or preparation of the manuscript. The specific roles of the authors are articulated in the ’author contributions’ section.