# Real-world database evaluation of drug-associated vitreous opacities and machine learning for clinical interpretability

## TL;DR

This study uses real-world data and machine learning to identify drugs linked to vitreous opacities and highlights strategies to prevent related complications.

## Contribution

The first systematic real-world evaluation of drug-associated vitreous opacities using FAERS data and machine learning for clinical interpretability.

## Key findings

- 38 drugs were identified as independent risk factors for vitreous opacities, primarily ocular, oncologic, hormonal, antimicrobial, and immunologic agents.
- Antimicrobial drugs had the earliest onset of vitreous opacities, while hormonal drugs had the latest.
- The BAG model showed higher sensitivity, with dexamethasone, brolucizumab, and other drugs as top predictors of vitreous opacities.

## Abstract

With visual disturbances from vitreous opacities (VOs) and floaters drawing increasing attention, we analyzed real-world data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to characterize VO-associated drug profiles and inform clinical strategies for reducing VO-related complications.

Disproportionality analysis was performed on FAERS reports (2004–2024) to identify VO-associated drugs. Drugs were then classified to assess the onset time and baseline characteristics. Multivariable logistic regression was used to evaluate confounders. The predictive performance was compared using six machine learning algorithms, with SHapley Additive exPlanations (SHAP) used for feature importance.

Among 3,817 VO-related reports, 38 drugs were identified as independent risk factors, and they were mainly ocular, oncologic, hormonal, antimicrobial, and immunologic agents. Antimicrobial drugs had the earliest onset (mean 43.6 days), and hormonal drugs had the latest (mean 409.2 days). In the bootstrapped aggregating (BAG) model, the top predictors of VO were dexamethasone, reporter, time, brolucizumab, and age. The five highest-risk drugs were dexamethasone, brolucizumab, triamcinolone, faricimab, and fingolimod.

This first systematic real-world evaluation of VO-related adverse drug reactions identifies high-risk drugs, susceptible populations, and onset patterns, thus offering guidance for preventive medication strategies. The BAG model showed higher sensitivity in real-world analysis, suggesting potential for further research in VO and floater prevention and treatment.