Research on IFIS Continues to Grow

New studies focus on causes, treatments and surgeon awareness.

By Jerry Helzner, Senior Editor

Intraoperative floppy iris syndrome (IFIS) during cataract surgery was first identified by the highly respected cataract surgeons Drs. David F. Chang and John Campbell in a landmark article published in the Journal of Cataract and Refractive Surgery in April 2005. At that time, Drs. Chang and Campbell primarily made the key association between tamsulosin (major brand Flomax) taken to promote urinary flow and the risk of IFIS.

In the intervening years, studies led by Kristiana D. Neff of the Storm Eye Institute, Charleston, S.C., and others have confirmed that tamsulosin is, by far, the key culprit in causing IFIS.¹ Other alpha blockers such as alfuzosin (Uroxatral) and doxazosin (Cardura) have also been implicated in causing the syndrome, but at a much lower incidence rate than tamsulosin.

However, as research into IFIS continues, some recent studies have been exploring the possibility that the constricted pupils, iris billowing and iris prolapse common to IFIS can also be triggered by other drugs and physical conditions that are totally unrelated to the taking of alpha blockers.

Additional Causes of IFIS

For example, at this year's ARVO meeting, research teams from the University of Texas Medical Branch in Galveston presented two highly interesting studies, one linking IFIS to patients taking warfarin (major brand Coumadin) and the other associating the occurrence of IFIS to patients with a history of cardiovascular disease.^2,3

In the case of warfarin, the researchers identified nine eyes of patients ages 64 to 82 who had taken warfarin (but did not take an alpha blocker) prior to cataract surgery. Of those nine eyes, seven exhibited severe to very severe IFIS during the procedure but were effectively managed with intraoperative placement of iris hooks.

With regards to cardiovascular disease, researchers did a retrospective study of 200 eyes of 144 patients who had cataract surgery performed by one surgeon in a one-year period. The researchers found that patients with hypertension had more than twice the risk of developing IFIS than non-hypertensive patients. Hypertension combined with different cardiovascular diseases such as atrial fibrillation, congestive heart failure and coronary artery/peripheral vascular disease increased the risk of IFIS even more. When hypertension was combined with the same patient taking tamsulosin, the incidence of IFIS was found to be 100% in the study group.

IFIS has primarily been linked to tamsulosin but recent research has uncovered other causes of the syndrome.

Both studies indicated the need for careful preoperative screening to identify patients taking alpha blockers or warfarin, or who have hypertension or cardiovascular disease.

Asked by Ophthalmology Management to comment on the new studies citing additional causes of IFIS, Dr. Chang offered the following:

“Neff and co-authors published a study in Ophthalmology in 2009 in which they identified a number of patients manifesting IFIS with no prior history of tamsulosin or other alpha blocker usage. In essence, this means that we should consider any patient with a small pupil as potentially having IFIS. Dr. Steven Dewey has made this point, and many of us no longer do pupil stretching for small-pupil management because of this. However, in my experience, severe IFIS is still most likely seen with tamsulosin and not as much with non-selective alpha antagonists. I am therefore much more likely to use iris retractors or a Malyugin ring with patients taking tamsulosin.”

Effective Treatment Reported

In the area of combating the symptoms of IFIS, Spanish researchers, reporting in a recent online edition of the journal Ophthalmology, conducted a study of 42 cataract surgery patients who had been taking the drug tamsulosin, primarily to facilitate urine flow.⁴

One eye of each patient was randomized to receive 0.6 ml of non-preserved bisulfite-free intracameral phenylephrine (IPH) 1.5% (group one) or balanced saline solution (group two) at the start of surgery. If significant miosis or iris prolapse occurred, IPH was injected during phacoemulsification in group two. No changes were performed in the surgeon's standard fluidic parameters or viscoelastic preferences.

Signs of IFIS were observed in 88.09% of eyes in group two. No signs of IFIS were noted in group one. Significant miosis, iris prolapse or both occurred in 54.76% of eyes in group two, although the condition was successfully reverted with IPH, with a significant increase in pupil size after IPH administration (from 4.77±0.88 mm to 6.68±0.93 mm). No intraoperative complications occurred.

The researchers concluded that intracameral phenylephrine is a highly efficient measure for prophylaxis against IFIS. Moreover, they said, the drug can reverse IFIS, restoring iris rigidity and causing the pupil to return to its preoperative size.

Though outside the parameters of this study, cataract surgeons have generally used a variety of pharmacologic and mechanical methods to prevent and combat IFIS. These include dilating drops, lidocaine and epinephrine on the pharmacologic side, and viscolelastics, iris hooks and pupil-expanding devices such as the Malyugin ring on the device side.

The Value of IFIS Awareness

Finally, a study of a large number of cataract surgery patients who had their procedures at the Veterans Affairs New York Harbor Healthcare System between 2000 and 2010 showed a strong correlation between surgeons' awareness of the risk of IFIS and better outcomes.

The study, presented at this year's ARVO meeting, included two large cohorts of patients. One cohort took alpha receptor agonists (such as Flomax) — and then had their surgery — before mid-2005, when intraoperative floppy iris syndrome was first identified. Another large cohort took alpha receptor agonists but had their procedure after warnings about IFIS were widely disseminated. The study sought to determine if outcomes for these resident-performed procedures improved once the surgeons were aware of the link between alpha receptor agonists and IFIS.⁵

Researchers from the VA Medical Center and Columbia University found that being able to identify those patients who had taken alpha receptor agonists prior to surgery and being aware of the potential for IFIS did improve overall outcomes. The results showed that vitreous loss was 11.6% in the cohort operated on prior to May 1, 2005, and only 3.5% in the group operated on after May 1, 2005. The probability of achieving a BCVA of 20/40 or better in the postoperative period was 82.7% (178/215) in the earlier group vs. 88.1% (201/228) in the later group.

The researchers concluded that “we believe that the improved outcomes are a result of heightened awareness of intraoperative floppy iris syndrome, implementation of IFIS prophylaxis techniques including preoperative atropine, intracameral epinephrine, the use of iris stabilization devices (such as iris hooks and Malyugin rings) and improved phacoemulsification techniques. The description of IFIS and implementation of prophylactic measures have resulted in improved outcomes in resident performed phacoemulsification in patients exposed to alpha receptor blockers.” OM

References

1. Neff KD, Sandoval HP, Fernández de Castro LE, Nowacki AS, Vroman DT, Solomon KD. Factors associated with intraoperative floppy iris syndrome. Ophthalmology. 2009;116:658-663.
2. Rasha AI, Alsheikh, O. Intraoperative floppy iris syndrome: An association with warfarin. ARVO 2012 (abstract).
3. Tung CI, et al. Hypertension complicated by cardiovascular disease is an important risk factor for the development of IFIS. ARVO 2012 (abstract).
4. Lorente R, de Rojas V, Vázquez de Parga P. Intracameral phenylephrine 1.5% for prophylaxis against IFIS: Prospective, randomized fellow eye study. Ophthalmology. 2012 Jun 16. [Epub ahead of print].
5. Neren A., et al. A Comparison of the outcomes of resident-performed phacoemulsification in patients on alpha blockers before and after the description of floppy iris syndrome (IFIS). ARVO 2012 (abstract).