Overview
Intraoperative floppy iris syndrome (IFIS) was first characterized by Chang and Campbell in 2005. It is associated with the use of systemic α-receptor blockers, such as tamsulosin (Flomax), used in the medical management of benign prostatic hyperplasia (BPH). The features of IFIS are seen during cataract surgery despite proper wound construction and compose of a triad of: (1) a flaccid iris that billows in response to normal intraoperative fluid currents; (2) a strong propensity for the iris to prolapse through any or all properly constructed incisions; and (3) progressive intraoperative pupillary constriction. This behavior of the iris creates a difficult situation for the surgeon and can potentially increase the complication rate. About 2% of the general cataract surgery population has some degree of IFIS. Since the syndrome was first described, surgeons have devised a variety of techniques to minimize the characteristics of IFIS.
Pharmacology
The iris is a complex structure mediated by the iris dilator smooth muscle and the sphincter muscle. When the α-receptors are stimulated, the dilator smooth muscle contracts to cause pupillary dilation, and conversely, when the α-receptors are blocked, the dilator smooth muscle relaxes, causing pupillary miosis. There are nine subtypes of α-receptors: α 1a , α 1b , α 1d , α 2a , α 2b , α 2c , ß 1 , ß 2 , and ß 3 . Like most tissues, multiple subtypes of adrenergic receptors exist in the iris smooth muscle. However, iris contraction is 100-fold more sensitive to α 1 -antagonists than α 2 -antagonists, which suggests that α 1 -receptors predominate in mediating dilation. Molecular, protein, and functional assays have found that the α 1a -receptor subtype mediates iris dilator smooth-muscle contraction in animal species. It is presumed that humans have a similar α 1a -receptor profile in the iris dilator muscle.
Like the iris, the prostate smooth muscle is also mediated by a balance of sympathetic, parasympathetic, and other receptor systems ( Box 36.1 ). BPH is associated with lower urinary tract symptoms such as nocturia, dysuria, and incomplete bladder emptying. The main α 1 -receptor subtype found in the smooth muscle of the prostate, urethra, and bladder neck is the α 1a -receptor. Blockage of the α 1a -receptor relaxes the prostatic smooth muscle to relieve outflow obstruction, and enhances urine flow. Older α 1 -receptor blockers such as alfuzosin (Uroxatral), doxazosin (Cardura), and terazosin (Hytrin) bind all α 1 subtypes equally. Tamsulosin (Flomax) is more uroselective, as it selectively binds α 1a and α 1d -receptors. However, because tamsulosin is a systemic drug, it is also selective for the iris dilator smooth muscle.
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Tamsulosin (Flomax) is a highly selective α 1a -receptor blocker
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α 1 -receptor blockade relaxes the iris dilator smooth muscle, causing miosis
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There is a broad continuum in the manifestation of the features of intraoperative floppy iris syndrome, with variation even between the eyes of the same patient
It is presumed that the lack of tone in the dilator muscle of the iris due to the highly selective α 1a -receptor blockade is responsible for the signs of IFIS. However, several studies have found that only a portion of patients on tamsulosin develop the manifestations of IFIS, and that there is a continuum of the degree of manifestation. Of patients taking tamsulosin, the percentage of eyes of patients with no IFIS features has been found to range from 10% to 43%. The percentage of eyes with all three characteristics of IFIS, or severe IFIS, has been reported as 30–43%. Manivikar and Allen found that 31% of eyes were well dilated and remained so throughout the surgery, 22% were well dilated but constricted during the surgery, 38% were mid dilated and remained the same or constricted further during the surgery, and 9% were poorly dilated at the outset. IFIS can present in varying degrees even between the two eyes of the same patient. Complete IFIS has been reported to occur in the eye of one patient, when surgery in the fellow eye 1 week prior did not reveal any IFIS.
While IFIS is clearly associated with tamsulosin, it is unclear whether or not other medications or systemic conditions can manifest an IFIS-like picture. Because the nonselective α-blockers have some affinity for the α 1a -receptor, one can presume that these medications may cause a minor degree of IFIS; however, multiple studies have not found an association between the nonselective α-blockers and IFIS. It is possible that other medications may cause IFIS. Zuclopenthixol, an antipsychotic with dopaminergic, as well as α-adrenergic blockade, may be associated with IFIS. However, this was found in just one patient, and thus warrants further study. Patients with diabetes and pseudoexfoliation syndrome can have poor dilation; however, these disease processes have not been implicated in IFIS. Similarly, pilocarpine, a muscarinic receptor antagonist, which causes miosis, has not been associated with IFIS. Furthermore, it has been reported that patients may develop IFIS without any known reason. There may be other issues at play in IFIS besides a simple α 1a -blockade of the iris dilator muscle.
Preoperative intervention
Many solutions have been proposed to minimize the effects of IFIS. The first seemingly obvious solution was to remove the offending medication. The half-life of tamsulosin is 48–72 hours. Stopping tamsulosin use prior to cataract surgery may have a slight effect on improving preoperative dilation, but does not affect IFIS severity. Patients have been reported to have varying degrees of IFIS even if they had not taken tamsulosin for 1–10 years. It is thought that a relatively constant α 1a -receptor blockade while patients are on tamsulosin therapy can lead to disuse atrophy of the iris smooth muscle. A lack of iris rigidity would explain the billowing of the iris to the point of prolapse through all wounds. The progressive miosis may be the natural response of the iris to its own billowing in the midst of normal irrigation currents. It is not known how long patients have to be taking tamsulosin before exhibiting the features of IFIS. It has been reported to occur after 3 months of use, but there have been anecdotal reports of occurrence after less than 1 month of therapy. Currently, most surgeons do not advocate discontinuing the drug before cataract surgery because of lack of evidence of any benefit ( Box 36.2 ).
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Stopping tamsulosin preoperatively does not affect the severity of intraoperative floppy iris syndrome
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Previous use of tamsulosin even years before surgery does not eliminate the manifestation of intraoperative floppy iris syndrome
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