BERKELEY, CA (UroToday.com) - The discovery that tamsulosin was associated with a new complication called intraoperative floppy iris syndrome (IFIS) solved a problematic mystery for cataract surgeons. Characterized by sudden intraoperative iris prolapse and pupil constriction, IFIS caused a significant increase in surgical complications when it was not recognized, understood, or anticipated.[1, 2, 3, 4, 5, 6] Sight threatening complications included retinal detachment, lost lens fragments, endophthalmitis, and severe iris defects associated with permanent pupil deformity, glare, and photophobia.[5, 6]
Of the alpha-1 receptor sub-types, the 1A receptor predominates in both the iris dilator and prostatic smooth muscle. Among alpha-1 antagonists prescribed for benign prostatic hyperplasia (BPH), only tamsulosin and silodosin are sub-type selective and demonstrate the highest affinity for the alpha-1A receptor. All of the alpha-1 antagonists can impair pupil dilation and cause IFIS. However, a number of prospective and retrospective studies surprisingly suggest that the frequency and severity of IFIS is greater in patients taking tamsulosin compared to the non-selective alpha-1 antagonists, such as terazosin, doxazosin, and alfuzosin.[1, 2, 3, 4, 5, 6, 7, 8, 9, 10] A 2011 meta-analysis of 17 published studies reported that tamsulosin had a 40-fold higher pooled odds ratio for IFIS compared to alfuzosin and terazosin. In vitro experiments demonstrated that tamsulosin is a much stronger antagonist of rabbit iris dilator muscle contraction than alfuzosin. Finally, a 2008 survey of members of the American Society of Cataract and Refractive Surgery (ASCRS) indicated that 90%* of the approximately 1 000 respondents felt that IFIS was more common with tamsulosin than with non-selective alpha-1 antagonists.
Because many of the prior studies were retrospective and were not masked, we decided to conduct a multicenter prospective, masked, controlled comparison of tamsulosin and alfuzosin - the two alpha-1 antagonists with the fewest reported cardiovascular adverse events. The study was conducted in France, where alfuzosin is more commonly prescribed than in most other countries. The study surgeons enrolled 113 consecutive patients taking either tamsulosin or alfuzosin. Each time a study patient was enrolled, a control patient with no prior history of alpha-1 antagonist use was enrolled by the same cataract surgeon on the same day. All 226 cases were videotaped and two masked ophthalmologists then graded the videos for the presence and severity of IFIS. Severe IFIS—defined as iris billowing and prolapse with ≥ 2 mm of pupil constriction—was noted in 34.3 percent (24/70) of the tamsulosin eyes and 16.3 percent (7/43) of the alfuzosin eyes (P < 0.05).
Another unexpected finding is that IFIS can still occur more than one year after tamsulosin has been discontinued.[1, 6, 9] Ninety-five percent* of ASCRS survey respondents have experienced IFIS in patients with a past history of alpha-1 antagonist use9. Because stopping alpha blockers pre-operatively is of questionable benefit, only 11% of survey respondents routinely discontinue tamsulosin prior to cataract surgery.
Why does tamsulosin have a greater effect on the iris than nonselective alpha-1 antagonists? Moreover, why does IFIS persist despite discontinuation of the drug? Histopathologic analysis of autopsy eyes from tamsulosin patients shows atrophy of the iris dilator muscle, which would be consistent with a semi-permanent drug effect. The first in vitro study of alpha-1 antagonist pharmacokinetics in the iris dilator muscle suggested that the mechanism of muscle inhibition by tamsulosin was more complex than simple receptor blockade8. Other evidence indicates that tamsulosin has a strong binding affinity for iris pigment granules. Based on histopathologic studies of rabbit iris dilator muscle, concentration of tamsulosin in the iris pigment granules may cause a long-term ‘toxic’ effect on the adjacent iris dilator muscle, which then atrophies.
Ophthalmologists should now anticipate IFIS by eliciting a history of current or prior systemic alpha-1 antagonist use, and a number of alternative surgical strategies can be used to improve outcomes in these cases.[1, 2, 6] Despite this, however, 95% of the ASCRS survey respondents believe that tamsulosin still increases the difficulty of cataract surgery and 77% believe that it increases the risks. This might explain why nearly 2 out of 3 respondents would avoid tamsulosin if they themselves had a mildly symptomatic cataract. This group would either take a non-selective alpha-1 antagonist, avoid alpha-1 antagonists altogether, or have their mildly symptomatic cataract removed first.
What should prescribing doctors consider? The prospect of IFIS is but one of many considerations for patients who might benefit from systemic alpha-1 antagonists, but also have cataracts. The two largest global ophthalmology organizations – ASCRS and the American Academy of Ophthalmology (AAO) –issued a joint IFIS educational statement in 2008 asking prescribing physicians to consider involving the ophthalmologist prior to initiating alpha-1 antagonists in patients with known cataracts. In addition, patients already taking systemic alpha-1 antagonists should be reminded to report this medication history prior to having any eye surgery. More recently, ASCRS and AAO have issued an updated joint advisory statement intended to better educate prescribing physicians about IFIS. This was in part motivated by a recent survey of primary care physicians at the University of California at San Francisco, which showed that only 35% were aware that alpha-1 antagonists can cause cataract surgical complications, and only half (17%) factored this into treatment considerations.
Considering the prevalence of both cataracts and BPH, many ophthalmologists worry about the prospect of increasing numbers of challenging IFIS cases as our population ages. Cataract surgery has long been the most frequent of all operations performed in the United States, and tamsulosin continues to be the most widely prescribed medical treatment for BPH. With the goal of reducing cataract surgical complications, ophthalmologists welcome the opportunity to be a resource for you and our mutual patients on this issue.
*excluding those with insufficient experience to know
- Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin (Flomax). J Cataract Refract Surg 2005; 31: 664-673.
- Chang DF, Osher RH, Wang L, Koch DD. A prospective multicenter evaluation of cataract surgery in patients taking tamsulosin (Flomax). Ophthalmology 2007; 114:957-964.
- Chadha V, Borooah S, Tey A, et al. Floppy iris behaviour during cataract surgery: associations and variations. Br J Ophthalmol. 2007; 91:40-42.
- Blouin M, Blouin J, Perreault S, et al. Intraoperative floppy iris syndrome associated with Alpha-1 adrenoreceptors. Comparison of tamsulosin and alfuzosin. J Cataract Refract Surg 2007; 33:1227-1234.
- Bell CM, Hatch WW, Fischer HD, et al. Association between tamsulosin and serious ophthalmic adverse events in older men following cataract surgery. JAMA 2009;301(19):1991-1996.
- Chang DF, Braga-Mele R, Mamalis N, et al. ASCRS white paper: clinical review of intraoperative floppy-iris syndrome. J Cataract Refract Surg 2008;34:2153-2162.
- Chatziralli IP, Sergentanis TN. Risk Factors for intraoperative floppy iris syndrome: A meta-analysis. Ophthalmology 2011; 118:730-735.
- Palea S, Chang DF, Rekik M, et al. Comparative effect of alfuzosin and tamsulosin on the contractile response of isolated rabbit prostatic and iris dilator smooth muscles. Possible model for intraoperative floppy iris syndrome. J Cataract Refract Surg 2008; 34: 489-496.
- Chang DF, Braga-mele R, Mamalis N, et al. Clinical experience with intraoperative floppy-iris syndrome. Results of the 2008 ASCRS member survey. J Cataract Refract Surg 2008; 34:1201-1209.
- Casuccio A, Cillino G, Pavone C, et al. Pharmacologic pupil dilation as a predictive test for the risk of intraoperative floppy-iris syndrome. J Cataract Refract Surg 2011;37: 1447-1454.
- Chang DF, Campbell JR, Colin J, Schweitzer C. Prospective masked comparison of intraoperative floppy iris syndrome severity with tamsulosin versus alfuzosin. Ophthalmology 2014;121: 829-834.
- Santaella RM, Destafeno JJ, Stinnett SS, et al. The effect of alpha1-adrenergic receptor antagonist tamsulosin (Flomax) on iris dilator smooth muscle anatomy. Ophthalmology 2010;117:1743-1749.
- Goseki T, Ishikawa H, Ogasawara S, et al. Effects of tamsulosin and silodisin on isolated albina and pigmented rabbit iris dilators – Possible mechanism of IFIS. J Cataract Refract Surg 2012;38: 1643-1649.
- Doss EL, Potter MB, Chang DF. Primary Care Physicians Still Lack Awareness of IFIS. J Cataract Refract Surg 2014;40: 685-686.
David F. Chang, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Dr. Chang is clinical professor at the University of California, San Francisco, and immediate past president of the ASCRS. He has no financial interest in this subject.
Click HERE to read a related joint press release from the American Society of Cataract and Refractive Surgery and the American Academy of Ophthalmology.