BPH Medications and Intraoperative Floppy Iris Syndrome

Benign prostatic hyperplasia or BPH is a common disorder in older men, and typically presents with symptoms of urinary hesitancy, weak stream, nocturia, incontinence and recurrent urinary tract infections.¹   Treatment options for this condition include alpha blockers, 5-alpha reductase inhibitors, alternative therapies such as saw palmetto extract, and surgical intervention such as transurethral resection of the prostate (TURP).  Alpha-receptor antagonists, a popular class of medication, promote smooth muscle relaxation by inhibiting smooth muscle contraction in the prostatic urethra.¹   This class of medication works well for moderate to severe BPH symptoms, and is divided into two categories: selective and non-selective agents.  Non-selective agents also inhibit alpha-adrenergic receptors  in the smooth muscle of the vasculature, and therefore reduce blood pressure, but have the undesirable side-effect of orthostatic hypotension.  Non-selective agents include doxazosin (Cardura), terazosin (Hytrin), and prazosin (Minipress).  In an effort to improve the side effect profile of this class of medication, selective alpha-antagonists were designed, which do not affect blood pressure.  Selective agents include tamsulosin (Flomax) and alfuzosin (Uroxatral).  Tamsulosin is an alpha-1A-adrenergic receptor antagonist.  In 2005, Chang and Campbell described an unusual syndrome during cataract surgery characterized by a flaccid iris leading to billowing of the iris, a tendency for the iris to prolapse through surgical incisions, and progressive pupillary constriction limiting visualization during surgery.  They termed this syndrome Intraoperative Floppy Iris Syndrome or IFIS.²   This syndrome can occur with any of the alpha-antagonists, but is particularly common with tamsulosin, and is speculated to be due to a high concentration of alpha-1A receptors in the iris dilator smooth muscle which, when inhibited, leads to deficient muscle tone.³  A meta-analysis performed in 2011 showed that the odds ratio for IFIS was 40-fold higher with tamsulosin than that of alfuzosin, which is the agent next most commonly associated with the syndrome², and a retrospective study reported that 86% of patients using Tamsulosin had IFIS compared to 15% of patients using alfuzosin⁵.  This syndrome is of particular concern to ophthalmologists,  because it increases the risk of complications during cataract surgery, including iris trauma, dropped lens fragments, and posterior capsular rupture.  Two issues make this situation even more complicated: at present, there is no reliable way to predict those patients who will develop IFIS prior to surgery, and the syndrome can occur despite stopping the medication.  In fact, there is no evidence that stopping the medication prior to surgery is of any benefit, and cases of IFIS have been reported as long as a year after stopping therapy.⁴  This raises the question of how to best address the issue.  At present, there are two recommendations put forth by ASCRS and the American Academy of Ophthalmology:⁴

      1.  Speak with the patient’s ophthalmologist before starting alpha-1 antagonists in patients with known cataracts, particularly if considering tamsulosin (Flomax)

      2.  Remind patients taking alpha-1 antagonists to report this medication to their ophthalmologist before having any eye surgery

Additionally, it may be reasonable to consider the class of 5-alpha reductase inhibitors such as Avodart (finasteride) and Proscar (dutasteride) first, or choose a nonselective alpha-antagonist before moving to a selective agent such as tamsulosin, given its very high incidence of associated IFIS.  While techniques and tools are available to help cataract surgeons reduce the risk of complications in patients with IFIS, the best option is to try and avoid the situation through planning and coordinated care.

1.   Diagnosis and management of benign prostatic hyperplasia.  Edwards JL.  Am Fam Physician. 2008 May 15;77(10):1403-10. Review.

2.  Risk factors for intraoperative floppy iris syndrome: a meta-analysis.  Chatziralli IP, Sergentanis TN.  Ophthalmology. 2011 Apr;118(4):730-5. Epub 2010 Dec 18.

3.   ASCRS White Paper: clinical review of intraoperative floppy-iris syndrome.  Chang DF, Braga-Mele R, Mamalis N, Masket S, Miller KM, Nichamin LD, Packard RB, Packer M; ASCRS Cataract Clinical Committee.  J Cataract Refract Surg. 2008 Dec;34(12):2153-62. Review.

4.   Floppy iris syndrome: why BPH treatment can complicate cataract surgery.  Chang DF.  Am Fam Physician. 2009 Jun 15;79(12):1051, 1055-6.

5.   Intraoperative floppy–iris syndrome associated with alpha1-adrenoreceptors: comparison of tamsulosin and alfuzosin.  Blouin MC, Blouin J, Perreault S, Lapointe A, Dragomir A.  J Cataract Refract Surg. 2007 Jul;33(7):1227-34.