Floppy iris syndrome risk: Study finds women more susceptible, key drugs identified

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Canadian researchers performed a large study to identify drugs that cause intraoperative floppy iris syndrome (IFIS) and they found that imipramine, tamsulosin, and chlorpromazine are the most frequent culprits, and women are more susceptible.¹ Moiz Lakhani, an MD candidate associated with the Faculty of Medicine, University of Ottawa, and The University of Ottawa Eye Institute, both in Ottawa, Ontario, Canada, and colleagues reported their findings in the American Journal of Ophthalmology.

Lakhani and colleagues explained that IFIS is associated with an increased rate of severe intraoperative complications and greater visual morbidity during cataract surgery, particularly in females; however, to now, no post-marketing pharmacovigilance study has comprehensively examined all FDA-approved drugs for their association with IFIS development or explored potential sex differences.

“Understanding the risk factors for IFIS allows cataract surgeons to better stratify surgical risks and implement appropriate preoperative and intraoperative measures to ensure adequate pupil dilation in high-risk patients,” they emphasized.

In their retrospective pharmacovigilance clinical cohort study, they analyzed cases in which IFIS developed and were reported to the FDA Adverse Event Reporting System (FAERS) from October 2003 to March 2024 using OpenVigil 2.1.

The authors used reporting odds ratios (RORs), proportional reporting ratios (PRRs), and relative risk reductions (RRRs), to assess signals for positive adverse reactions compared to all other drugs. They also conducted subgroup analyses based on patient gender.

The FAERS contained 12,345,128 reports of adverse events associated with more than 20,000 drugs. A total of 649 (0.0053%) cares had involved IFIS; over 75% of these adverse events had been reported by healthcare professionals.

“Drugs with the highest disproportionality for the development of IFIS included imipramine (ROR, 251.66, 95% confidence interval [CI], 157.53-402.02), tamsulosin (ROR, 171.44, 95% CI, 143.12-205.36), and chlorpromazine (ROR, 91.30, 95% CI, 49.91-167.03) (P<0.0001, for all comparisons),” Mr. Lakhani and colleagues reported.

They also identified over-reported drug classes involved in IFIS that included α1-blockers, tricyclic antidepressants, atypical antipsychotics, carbonic anhydrase inhibitors, corticosteroids, 5α-reductase inhibitors, β-blockers, prostaglandin analogs, and β2-agonists.

Among women, brinzolamide (ROR, 409.63, 95% CI, 196.78-852.73) and salbutamol (ROR, 67.12, 95% CI, 28.37-158.80) were disproportionately associated with IFIS (P<0.0001 for both comparisons); these associations were not observed in males.

In commenting on their findings, the investigators concluded, “This analysis of over 20,000 drugs and 12 million reports highlights that, in addition to α1-blockers and atypical antipsychotics, tricyclic antidepressants are among the key agents most disproportionately associated with IFIS, with notable sex differences. These findings are crucial for informing perioperative counseling and surgical planning for cataract surgery.”

Reference

1. Lakhani M, Kwan ATH, Mihalache A, et al. A real-world population-based study drugs associated with floppy iris syndrome. Am J Ophthalmol. 2025; published online March 18, 2025; published online March 18, 2025. Doi:10.1016/j.ajo.2025.03.023