Antibiotic Exposure May Be Associated with AMD Development, Study Finds

Dimita Skondra, MD, PhD

Credit: University of Chicago

Antibiotic exposure may be associated with the development of new-onset age-related macular degeneration (AMD), according to new research.¹

The case-control study of more than 300,000 cases of AMD reported a frequency- and duration-dependence to the association, showing increased odds of AMD with a greater cumulative number of antibiotic prescriptions.

“Our results suggest that use of fewer prescriptions, limiting total days of exposure, and choosing agents with appropriately narrow coverage may be important components of antibiotic stewardship to prevent AMD development,” wrote the study authors, led by Dimita Skondra, MD, PhD, department of ophthalmology and visual science, University of Chicago Medicine.

The growing global use of antibiotics has raised concerns about antibiotic resistance, but a less recognized threat may be the impact of antibiotics on the human microbiome.² Microbial alterations resulting from antibiotic exposure have been linked to diseases in the developed world, including obesity and inflammatory bowel disease. Skondra and colleagues suggest AMD shares several features associated with these modern inflammatory diseases.

However, despite the inflammatory pathogenesis the study team indicates the association between antibiotic exposure and AMD development is largely unexplored in epidemiological data. Due to this gap in knowledge, the study team performed a large case-control study that compared antibiotic usage in those with new-onset AMD to matched controls from the general population.¹

These data were collected on cases aged 55 years and older with a new-onset International Classification of Diseases (ICD) diagnosis of AMD between 2008 and 2017 from the Merative MarketScan Commercial and Medicare Databases. The analysis summarized the cumulative number of prescriptions and day supply of antibiotics in the 24 months before the index visit.

To determine the relationship between AMD and antibiotic class, antibiotic spectrum, number of prescriptions, day supply, and the most prescribed antibiotic, the study team performed conditional univariate and multivariable logistic regression and adjusted for AMD risk factors.

Overall, the sample consisted of 312,404 cases and 312,376 controls, achieving statistical balance. Descriptive statistics indicated a greater percentage of cases were female, smokers, and diagnosed with diabetes, with an average age of 74.9 years for both cases and controls.

Multivariable analyses, adjusted for AMD risk factors, showed the greatest odds of a new-onset ICD code diagnosis of AMD with exposure to aminoglycosides (odds ratio [OR], 1.24; 95% CI, 1.22 - 1.26) and fluroquinolones (OR, 1.13; 95% CI, 1.12 - 1.14). Statistically significant associations were observed between dry and wet AMD and antibiotic use, with aminoglycosides and fluroquinolones each associated with greater odds of wet AMD

The analysis found the Increased odds of a new-onset ICD code diagnosis of AMD were approximately three times greater for broad-spectrum antibiotics (OR, 1.15; 95% CI, 1.13–1.16) compared to narrow-spectrum antibiotics (OR, 1.05; 95% CI, 1.03–1.07). Investigators also observed a frequency- and duration-dependent association between antibiotic use and a new-onset diagnosis of AMD.

A single prescription of antibiotics increased the odds of new-onset AMD by 7% (OR, 1.07; 95% CI, 1.06 - 1.09) and each additional prescription increased the odds by nearly 4%. In addition, 1–7-day and 8–14-day antibiotic supplies increased the odds of AMD by 5%, with additionally day supply further increasing those odds.

“These findings support the hypothesis that larger perturbations to the gut microbiome, triggered by either broader antibiotic coverage or greater cumulative exposure, may increase the odds of developing AMD,” investigators wrote.

References

1. Moir J, Hyman M, Wang J, Flores A, Skondra D. The Association of Antibiotic Use and the Odds of a New-Onset ICD Code Diagnosis of Age-Related Macular Degeneration: A Large National Case-Control Study. Invest Ophthalmol Vis Sci. 2023;64(12):14. doi:10.1167/iovs.64.12.14
2. Klein EY, Van Boeckel TP, Martinez EM, et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proc Natl Acad Sci USA. 2018;115(15):E3463–E3470