New findings published in Investigative Ophthalmology & Visual Science sought to elucidate the relationship between antibiotic exposure and new-onset diagnosis of age-related macular degeneration (AMD).
Give me some background first.
Considering the broad use of antibiotics, one common concern of clinicians and researchers is the rise of antibiotic resistance.
However, another clinical challenge is that antibiotics may change the composition and diversity of the human microbiome—especially in industrialized countries with prevalent antibiotic use.
Go on…
This change in microbiome may be responsible for the emergence and progression of diseases such as obesity, type 2 diabetes, metabolic syndrome, and asthma.
AMD shares several commonalities with these diseases, namely its ubiquity in industrialized regions around the world.
This motivated a research team from the University of Chicago to investigate gut microbiome health in relation to AMD diagnosis and the concept of the “gut-retina axis.”
Now, talk about the study.
Researchers performed a case-control study of 312,404 patients aged 55 and above with new-onset AMD between 2008 and 2017 from the Merative MarketScan Commercial and Medicare databases and 312,376 matched controls from the general population.
They evaluated a series of associations between antibiotic usage in new-onset AMD patients, including:
- Timing of antibiotic prescription
- Various antibiotic classes, such as broad- vs. narrow-spectrum antibiotics
- Frequency-dependent associations measured by the cumulative number of antibiotic prescriptions and cumulative day supply of antibiotics
Findings?
Of the antibiotic classes, exposure to aminoglycosides (odds ratio [OR]=1.24, 95% confidence interval [CI] 1.22-1.26) and fluoroquinolones (OR=1.13, 95% CI 1.12-1.14) were associated with the greatest odds of new-onset diagnosis of AMD.
Tell me more about fluoroquinolone.
Further, exposure to fluoroquinolones in the 0-6 months preceding AMD diagnosis was associated with the greatest odds of a new-onset diagnosis of AMD compared to exposure at 6-12 months and 1-2 years.
This is potentially due to the fact that fluoroquinolones can mediate an acute inflammatory or cytotoxic effect that may accelerate AMD development in patients with a heightened baseline risk.
What about different classes of antibiotics?
Broad-spectrum antibiotics were associated with nearly three times greater odds of a new-onset diagnosis of AMD (OR=1.15, 95% CI 1.13-1.16) in comparison to narrow-spectrum antibiotics (OR=1.05, 95% CI 1.03-1.07).
And frequency-/duration-dependent associations?
The research team also identified a frequency- and duration-dependent association, with a greater cumulative number of antibiotic prescriptions or day supply of antibiotics conferring increased odds of new-onset diagnosis of AMD.
Were there any antibiotics that weren’t linked to AMD?
The study authors noted that three commonly prescribed antibiotics—including amoxicillin, azithromycin, and trimethoprim/sulfamethoxazole—did not increase or decrease the odds of AMD when administered as a single prescription.
Explain the “gut-retina axis.”
Taking a step back to look at the big picture, the term dysbiosis is defined as the imbalanced state where greater intestinal wall permeability could allow for translocation of microbial endotoxins, which may be possible sources and triggers of systemic inflammation.
The frequency- and duration-dependent association between antibiotics and AMD diagnosis may reflect a trend of sustained gut dysbiosis with inflammatory spikes or flares that eventually disseminate along the gut-retina axis.
Expert opinion?
According to the study authors, “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.”
Take home.
This study demonstrates that greater cumulative exposure to antibiotics—particularly fluoroquinolones, aminoglycosides, and those with broader-spectrum coverage—may be associated with the development of AMD.
Further population-level studies of multiple independent databases are required to confirm these findings.