Tamsulosin, an alpha blocker used to treat benign prostatic hyperplasia (BPH), has acquired attention far beyond the specialty of urology. Its capacity to relax iris dilator smooth muscle causes concern for ophthalmologists, who are often faced with floppy irides in patients on the drug and sometimes in patients on similar drugs as well.
Ninety-five percent of cataract surgeons believe that tamsulosin (Flomax) increases the difficulty of surgery, and 77 percent feel that it increases the risks, according to a 2008 survey conducted by the Cataract Clinical committee of the American Society of Cataract and Refractive Surgeons.1 David F. Chang, MD, chairman of that committee, reported on the survey at the Spotlight on Intraoperative Floppy Iris Syndrome (IFIS) symposium at the Joint Meeting of the Academy and the European Society of Ophthalmology in Atlanta. “Since IFIS was first reported nearly four years ago, surgeons now have the ability to recognize and anticipate it, and to employ a variety of specific surgical strategies to manage the floppy iris,” said Dr. Chang. “It was therefore very telling that 23 percent of the survey respondents still reported a higher incidence of posterior capsule rupture, and 52 percent reported a higher rate of significant iris damage during the previous two years in IFIS eyes.”
Why Not Stop Tamsulosin?
Advising patients to stop the drug prior to surgery may be of questionable value, according to information presented both in Atlanta and in a new white paper authored by the ASCRS Cataract Clinical committee.2 Dr. Chang noted that in a large multicenter prospective trial, stopping tamsulosin prior to surgery did not seem to lessen the rate or severity of IFIS.3 And among the survey respondents, 64 percent said that they never stop tamsulosin preoperatively, compared with only 11 percent who routinely do.
Debra A. Schwinn, MD, a leading authority on alpha receptors, addressed the Atlanta session on the pharmacology of IFIS and said that whether tamsulosin is discontinued prior to surgery depends on the surgeon’s comfort level and the patient’s willingness to stop. “Either approach can be used,” said Dr. Schwinn, who is professor and chairwoman of anesthesiology at the University of Washington in Seattle. She recommended either stopping about two weeks prior to surgery or, if continuing, using certain methods to deal with IFIS (see “A Stepwise Approach”).
She cautioned that if the surgeon plans to use atropine, then it would be wise not to stop the alpha blocker because the use of atropine without an alpha blocker could lead to acute urinary retention. But she added that this problem easily can be recognized by the patient and treated by the urologist. “So in the end, it depends on how the ophthalmologist plans to treat, or pre-treat to prevent, IFIS.”
From the urologist’s point of view, stopping alpha blockers prior to surgery, and then correctly restarting them, appears to pose little or no risk. “From our standpoint, patients may have some worsening of urinary symptoms but a low chance of major problems,” said Chad W. M. Ritenour, MD, at the IFIS Spotlight session. Dr. Ritenour is assistant professor of urology and director of the Men’s Health Center at Emory University in Atlanta. “Stopping the medicine, if it’s safer for the eye, is a more important thing to do.” But either way, he said, the urologist or primary care physician should be involved in the decision.
The Mechanism of IFIS
Tiago S. Prata, MD, a glaucoma fellow at the New York Eye and Ear Infirmary, also addressed the IFIS session, presenting OCT results of 29 patients taking tamsulosin. These showed significant thinning of the mid-iris stroma compared with control eyes.
And histopathologic evidence presented by Ricardo M. Santaella, MD, a fellow at Duke University in Durham, N.C., showed the iris dilator muscle in tamsulosin eyes was significantly thinner than control eyes. However, his retrospective study of 26 cadaver eyes from patients on tamsulosin noted no difference in the iris stromal thickness compared to 26 age-matched control eyes. “We believe this finding may shed light on the pathophysiology of IFIS and supports the hypothesis that alpha1A adrenergic receptor antagonism may lead to atrophy of the iris dilator muscle.” He continued, “We were trying to explore if tamsulosin leads to structural changes or atrophy of the iris dilator muscle. In our study, we did not find a significant correlation between total tamsulosin exposure and muscle thickness. Perhaps there is a dose independent effect from this alpha1A selective receptor antagonist on the muscle.”
Are All Alpha Antagonists Equal?
Dr. Schwinn said there are no data to support the “exoneration” of other alpha antagonists. “The FDA,” she said, “has declared IFIS to be a class drug effect, meaning that all alpha1 blockers are capable of inducing IFIS.”
However, Dr. Chang noted that there are approximately a half-dozen retrospective and prospective clinical studies suggesting that IFIS is more likely to occur with tamsulosin than various nonselective alpha antagonists and that these were mentioned in the ASCRS white paper. Tamsulosin is selective for the alpha1A receptor subtype, whereas alfuzosin (Uroxatral), doxazosin (Cardura) and terazosin (Hytrin) are nonsubtype-selective antagonists. Dr. Chang also said that among those respondents in the ASCRS survey with sufficient experience, 90 percent felt that IFIS was more likely to occur with tamsulosin, and two-thirds felt that is was “much more likely” than with other alpha blockers.
Dr. Chang said it may therefore make sense for patients with early cataracts who have not yet begun treatment for BPH to start with a 5-alpha reductase inhibitor—finasteride (Proscar) or dutasteride (Avodart)—or a nonselective alpha1 antagonist. Alfuzosin is also uroselective but appears to have a lower tendency to cause IFIS. In one retrospective study, 86 percent of patients on tamsulosin had IFIS compared with only 15 percent on alfuzosin.4 Dr. Ritenour said that no single alpha blocker has been proven superior in the treatment of BPH symptoms and that patients are typically offered different agents if the first is not effective enough.
Though stopping tamsulosin preoperatively is of uncertain benefit, Steve A. Arshinoff, MD, prepared a letter for patients and the tamsulosin-prescribing doctor, suggesting a switch to one of the drugs less associated with IFIS. Dr. Arshinoff is in private practice in Toronto. “If another drug is as good for their urinary symptoms, they could consider taking that one instead,” he said. Dr. Chang noted that a new drug, silodosin (Rapaflo), was recently approved for BPH. “This alpha blocker most closely resembles tamsulosin in that it is selective for the alpha1A receptor subtype.”
A Stepwise Approach
When dealing with IFIS there are two things the surgeon does not want to do: sphincterotomies and pupil stretching, said Dr. Chang. In IFIS, the pupil immediately snaps back to its original size following attempts to stretch it. Instead, he urges surgeons to consider a variety of strategies in a stepwise approach, such as that outlined by Uday Devgan, MD, who spoke at the Atlanta session. Dr. Devgan is an associate clinical professor at the University of California, Los Angeles, and chief of ophthalmology at the Olive View UCLA Medical Center.
1. Pharmacologic Tx. Although many cataract surgeons start with iris hooks or expansion rings to dilate the pupil, Dr. Devgan first tries pharmacologic approaches, including preoperative atropine and intracameral epinephrine or phenylephrine. He favors a solution devised by the late Joel Shugar: a blend of 3 cc of preservative-free lidocaine 4 percent, 9 cc of BSS plus, and 4 cc of 1:1,000 preservative-free epinephrine, which gives a neutral solution of pH 7 containing 0.75 percent lidocaine and 1:4,000 epinephrine. Inject the “epi-Shugarcaine” under the iris, he said, and within 20 seconds the pupil should dilate and iris tone increase.
2. Viscoelastic Tx. If the pharmacologic treatment alone doesn’t work, Dr. Devgan proceeds to a high-viscosity ophthalmic viscosurgical device (OVD) to stabilize the tissue, create space in the anterior segment and balance pressure in the anterior and posterior chambers. This creates high pressure both in front of and behind the iris. “It’s important to select a super cohesive viscoelastic agent such as Healon 5, which can create a solid plug or barrier on top of the iris,” said Dr. Devgan.
Before creating the capsulorhexis, Dr. Arshinoff favors using two viscoelastics—Viscoat followed by Healon 5—and then balanced salt solution. The Healon 5 forms the rigid inferior surface of the OVD soft shell, while Viscoat tamponades the iris, keeping it stable during the procedure. “If you use one viscoelastic, you can’t achieve both functions,” he explained.
3. Mechanical Tx. “If you use viscoelastics intelligently, the number of patients who need rings is very low—maybe two percent of all these cases,” Dr. Arshinoff said, and he added that it’s difficult to use a ring without first stabilizing the iris with an OVD. When the case does call for a mechanical device, Dr. Devgan favors the Malyugin ring because it always creates a round 6-mm pupil, holds the iris back and away from the phaco tip, doesn’t require additional incisions, is easy to use and is disposable. “It’s well worth the mild cost,” he said, adding that he has no financial interest in the product or its vendor, MST.
Dr. Chang said that mechanical devices, such as iris retractors, are still the most reliable method for dealing with IFIS. “Not everyone will be as comfortable with small pupil surgery as our session speakers, and it is often better to have the assurance that the pupil absolutely will not constrict,” he said. “This is particularly important with other complicating factors, such as dense lenses, pseudoexfoliation and one-eyed patients.”
Dr. Arshinoff also follows a stepwise approach. “If you follow the steps in logical order, it’s really easy to manage IFIS cases,” he said. First, in the office, preoperatively, he observes how much the pupil dilates in response to mydriacyl and 2.5 percent phenylephrine. There’s no problem with a pupil that dilates to 7 mm or more, he said, but if there’s a poor response, with the pupil dilating only to 6 mm or less, he recommends the viscoelastic soft-shell technique.5 “The whole point of this stepladder approach is that each step makes the subsequent step easier.”
1 J Cataract Refract Surg
2 J Cataract Refract Surg
4 J Cataract Refract Surg
5 J Cataract Refract Surg
___________________________ Dr. Arshinoff is a consultant to Alcon and Zeiss, and has consulted for all of the companies that manufacture viscoelastics. Dr. Chang’s AMO and Alcon consulting fees are donated to the Himalayan Cataract Project. Dr. Devgan is a consultant and stockholder of AMO. Dr. Ritenour reports no financial interests. Dr. Santaella’s research was supported by a grant from Research to Prevent Blindness. Dr. Schwinn reports no related interests.