April 2019


Research Highlight
Study shows IFIS cases more severe in females

by Vanessa Caceres EyeWorld Contributing Writer

Iris prolapse during hydrodissection in a patient taking tamsulosin
Source: David F. Chang, MD


You may be ever-vigilant about intraoperative floppy iris syndrome (IFIS) in male cataract patients of a certain age, but what about female patients?
A newly published study1 found that although IFIS was less common in females, it was associated with more intraoperative complications and worse visual outcomes.
Led by Argyrios Tzamalis, MD, researchers focused on male and female differences related to IFIS in cataract surgery patients. They wanted to address this because little has been published about IFIS differences in males versus females.
Their comparative, retrospective case control study included 3,811 eyes from 3,213 patients. All IFIS cases were classified as grade 0 (no progressive miosis, iris billowing, or iris prolapse observed), grade 1 (one of the three IFIS signs), grade 2 (two of the three signs), and grade 3 (all three IFIS signs). Risk factors related to IFIS were also noted, including pseudoexfoliation, glaucoma, ocular hypertension, and diabetic retinopathy.
All patients in the study had standardized preop dilation with tropicamide 0.5%, phenylephrine hydrochloride 2.5%, and cyclopentolate 1% drops. Topical anesthesia was performed with proparacaine hydrochloride 0.5% and intracameral anesthesia with an ophthalmic viscosurgical device. Cataract surgery was done with a 2.4 mm clear corneal incision and two side ports. Surgeons evaluated the final corrected distance visual acuity (CDVA) at a 2-month follow-up.
Among all patients, 50.8% were female. The mean patient age was 72.3 years.


The overall IFIS incidence in the study was 3.2%, which is in line with previous studies that have found a rate between 0 and 3.7%, according to the researchers. The incidence of IFIS was 5.17% in male patients (97 of 1,874 eyes) compared with 1.29% of female patients (25 of 1,937 eyes). Intraoperative floppy iris syndrome was significantly higher in male versus female patients (P<.0001).
Researchers did not find a significant age difference when comparing IFIS in males versus females. The use of alpha-1 receptor blockers was a risk factor in male patients but not females. Ocular risk factors typically associated with IFIS, such as glaucoma, ocular hypertension, and diabetic retinopathy, did not appear to influence the incidence of IFIS. Most male and female IFIS cases were operated on by senior surgeons. The only factor that appeared to influence IFIS was the use of alpha-1 receptor antagonists in males.
The incidence of posterior capsule rupture increased significantly by the appearance of IFIS (P<.0001). Severity grades were not significantly different between males (mean, 1.96) versus females (2.11).
However, there were some differences when IFIS occurred in females. “In a between-sex comparison of IFIS patients, the posterior capsule rupture rate was significantly higher in female patients than male patients,” the researchers wrote. All female IFIS cases had vitreous loss with posterior capsule ruptures, while the respective proportion in males was 78% among the posterior capsule rupture cases.
“The female sex was found to be a statistically significant risk factor for posterior capsule rupture, vitreous loss, and nucleus drop in cases in which IFIS occurred,” according to the researchers.
The male cases were better controlled with careful incision location and construction and use of less aggressive, low-flow phaco fluidic parameters, the researchers wrote. In contrast, female cases required use of more than one ophthalmic viscosurgical device, intracameral use of epinephrine, longer operating times, and anterior vitrectomy for posterior capsule rupture. “Male patients were also better briefed before surgery on the possible complications, and their anticipations were handled more efficiently compared with female IFIS patients,” they wrote.
There also were some differences in CDVA with glasses at 2 months in the female IFIS cases compared with females. Specifically, the CDVA was lower compared with non-IFIS cases. “The final CDVA (with spectacles) was found to be influenced by the IFIS severity grade only in females,” they wrote.

A few surprises

Dr. Tzamalis and his co-researchers were surprised by the findings. “The intraoperative complications rate in females was much higher, leading to a poorer final visual outcome,” he said. Despite the prevalence of experienced surgeons working with the cases, there was a markedly higher percentage of posterior capsule rupture, the authors noted.
Michael Greenwood, MD, was initially surprised by the results, until he thought about it a little more. “In hindsight, when you’re not expecting IFIS to come into play, it puts you more at risk for complications. It makes sense in the bigger picture,” he said.
Surgeons should remain vigilant about IFIS risk in males and females, both to avoid negative consequences if they are not managed properly and because a growing number of drugs seem to be associated with IFIS risk, surgeons said.
Dr. Tzamalis and co-researchers will publish results soon from a large multivariate regression analysis that analyzes systemic medications and their risk factors for the appearance of IFIS in women.

About the doctors
Michael Greenwood, MD
Vance Thompson Vision
Fargo, South Dakota

Argyrios Tzamalis, MD
Aristotle University of Thessaloniki Papageorgiou General Hospital
Thessaloniki, Greece

Contact information
: Michael.greenwood@vancethompsonvision.com
Tzamalis: argyriostzamalis@yahoo.com


1. Tzamalis A, et al. The role of sex in intraoperative floppy-iris syndrome. J Cataract Refract Surg. 2019;45:41–47.

Financial interests
: None
Tzamalis: None

Pearls to help lower the risk of IFIS

1. Consider IFIS risk in all patients
“Thorough current and previous medication use documentation, preoperative recognition of those at risk for developing IFIS, and the surgeon’s awareness in advance are all crucial in safely managing this condition,” Dr. Tzamalis said.

2. Think beyond tamsulosin
Although tamsulosin is the drug associated most closely with IFIS, there appears to be a growing list of other medications that can raise the risk, Dr. Greenwood said. Other medications associated with IFIS include finasteride, anti-psychotic agents, donepezil, duloxetine, labetalol, and herbal remedies like saw palmetto, according to the study from Dr. Tzamalis. It’s also important to keep the risk in mind because even a one-time use could increase the chance of IFIS occurring, Dr. Greenwood cautioned.

3. Use surgical tricks and techniques to avoid or manage IFIS
“Proper wound construction can help with other complications of IFIS, like having iris prolapse,” Dr. Greenwood said. There also is some evidence that pretreating with a nonsteroidal anti-inflammatory drug before cataract surgery can help stiffen the iris and lessen the effect of IFIS. Use of Omidria (phenylephrine/ketorolac, Omeros) intracamerally during cataract surgery can also lessen the effect, Dr. Greenwood said.

Study shows IFIS cases more severe in females Study shows IFIS cases more severe in females
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